Fabien Moinard-Butot (email)
Simon Nannini
Marie Pautas
Roberto Luigi Cazzato
Guillaume Virbel
Sophie Martin
Laure Pierard
Caroline Schuster
Inès Menoux
Mickael Burgy
Gabriel Malouf
Catherine Roy
Philippe Barthélémy
Methods: We included all patients with BM mRCC treated at the Institut de Cancérologie Strasbourg Europe (ICANS), in first-line with ICI based combinations. Bone radiological evolution according to RECIST v1.1, reviewed by an expert radiologist, as well as tissue osteolytic and/or osteocondensing character was assessed according to site of bone involvement (spinal column, sacrum, long bones), number of BMs (1, 2-5, >5), and immunotherapy-based combination.
Results: Between May 2015 and November 2023, we identified 38 patients with bone metastatic mRCC. The median age was 64 years old, 26 patients (68%) are male.Nineteen patients (50%) received an ICI-ICI combination, 17 patients (45%) ICI-TKI and 2 (5%) patients ICI alone. Fifteen patients (39%) had 1BMs, 15 patients (39%) had 2-5 BMs and 8 patients (22%) had >5 BMs. Patients with spinal column metastases had disease control in 67%, compared with 70% for sacrum metastases and 65% for long bones metastases. Fourteen patients (93%) with 1 BMs had disease control, 12 patients (80%) with 2-5 BMs and 3 patients (37%) with >5 BMs. Eleven (29%) developed bone condensation and/or bone reconstruction, with a median time to onset of 4.3 months. With a median follow-up of 45.8 months, only one patient with bone condensation progressed on bone.
Conclusion: The bone response in mCRC treated with ICI-based therapy appears to be a response according to RECIST v1.1, but also the early appearance of condensation-type bone changes.
Doi
https://doi.org/10.55788/e39fcc7b
Introduction
The incidence of bone metastasis (BM) in renal cell carcinoma (RCC) is around 30% 1. The most frequent locations are the spinal column, sacrum and proximal femur2. BMs are predominantly osteolytic leading to altered bone integrity and inducing significant morbidity for patients with high levels of skeletal-related events (SRE)3. SRE was defined as a pathological fracture, requirement for palliative radiotherapy or surgery to bone, hypercalcemia or spinal cord compression. In metastatic RCC (mRCC), 74-85% of patients experienced at least one SRE and impacted quality of life1.
BM is an independent poor prognostic factor for patients with mRCC4. In a study with 223 patients treated with sunitinib, progression-free survival and overall survival (OS) were significantly improved for patients without bone metastasis5. Ruatta et al. showed patients with less than 5 BM had a longer OS versus patients with >5 BM. Moreover, the location of BM had an impact on OS, with patients presenting BM located to long bones having better prognostic than patients with BM located to the spinal column or sacrum (28.6 months vs 19.7 months vs 17.6 months respectively, P<0.0001)6.
The treatment of RCC has been revolutionised by the advent of immunotherapy (ICI)-based combinations. ICI may be combined with either another ICI or a vascular endothelial growth factor pathway receptor (VEGFR) targeted therapy. These different combinations have shown benefits in terms of OS and overall response rate (ORR), compared with Sunitinib in several large randomised phase 3 trials7–10.
Some data suggest that ICI-TKI combinations are particularly effective against bone metastases, notably subgroup analyses of the CLEAR and CheckMate 9ER studies11,12. The aim is to monitor the efficacy of immunotherapy-based combinations on bone metastases, depending on their location and numbers.
Materials and methods
We performed a single-centre retrospective study of patients treated for mRCC with BM in first-line treatment with ICI-based therapy, from May 2015 to May 2023 at the Institut de Cancérologie Strasbourg Europe. Eligible patients had histologically confirmed clear cell Renal Cell Carcinoma treated with an ICI-based therapy combined with either an ICI or anti-VEGFR tyrosine kinase inhibitor (TKI) according to the standard approved schedule. The used protocols included: ipilimumab and nivolumab, pembrolizumab and axitinib, nivolumab and cabozantinib, pembrolizumab and lenvatinib. Dose reduction for toxicity, based on the standard recommendations for all agents, was permitted at the investigator’s discretion. No patient received specific bone-directed therapy like bisphosphonates or anti-RANKL therapy. The diagnosis and assessment of BMs were carried out on a CT scan. Exclusion criteria were non-clear cell carcinoma and patients treated with single-agent TKI.
Pre-treatment patient characteristics and laboratory data were collected. Demographic, clinical, and pathological data were also collected. Patients were characterised according to IMDC prognostic risk score13.
Endpoints
The primary endpoint was bone disease control rate (DCR) according to BM location (spinal column, sacrum, long bones). Bone DCR was defined as the percentage of patients with partial or complete response or stable disease on bone over the study period. DCR was reviewed and confirmed by a medical oncologist and an expert GU radiologist (RLC). The secondary endpoints included bone DCR according to BM number (1, 2-5, >5), and assessment of bone modifications (reconstruction, condensation). All data were exclusively obtained retrospectively, with no procedure taken to recover unavailable data by contacting healthcare providers or patients.
Statistical analysis
Descriptive statistics were utilised to summarise patient demographics, clinical characteristics, and treatment patterns. Categorical variables were expressed as frequency and percentage, and continuous variables as mean and standard deviation or median and range.
Results
Between May 2015 and May 2023, we identified 38 patients with bone metastatic RCC. The median age was 64 years old (range 43-92), and 26 patients (68%) were male. The IMDC score distribution was: 2 favourable (6%), 18 intermediate (47%), and 18 poor (47%) risk patients. Nineteen patients (50%) received an ICI-ICI combination, 17 patients (45%) ICI-TKI and 2 patients (5%) IO alone. Twenty-seven pts (71%) had spinal column metastases, 20 pts (53%) had sacrum metastases and 17 pts (45%) had long bone metastases. Fifteen pts (39%) had 1 BM, 15 pts (39%) had 2-5 BMs and 8 pts (22%) had >5 BMs (Table 1). Sixteen patients (42%) received local treatment of at least one metastatic site. The most frequent was radiotherapy for 6 patients (38%) (Table 1). No patient received specific bone-directed therapy.
Table 1: Patient characteristics
We performed a single-centre retrospective study of patients treated for mRCC with BM in first-line treatment with ICI-based therapy, from May 2015 to May 2023 at the Institut de Cancérologie Strasbourg Europe. Eligible patients had histologically confirmed clear cell Renal Cell Carcinoma treated with an ICI-based therapy combined with either an ICI or anti-VEGFR tyrosine kinase inhibitor (TKI) according to the standard approved schedule. The used protocols included: ipilimumab and nivolumab, pembrolizumab and axitinib, nivolumab and cabozantinib, pembrolizumab and lenvatinib. Dose reduction for toxicity, based on the standard recommendations for all agents, was permitted at the investigator’s discretion. No patient received specific bone-directed therapy like bisphosphonates or anti-RANKL therapy. The diagnosis and assessment of BMs were carried out on a CT scan. Exclusion criteria were non-clear cell carcinoma and patients treated with single-agent TKI.
Pre-treatment patient characteristics and laboratory data were collected. Demographic, clinical, and pathological data were also collected. Patients were characterised according to IMDC prognostic risk score13.
Endpoints
The primary endpoint was bone disease control rate (DCR) according to BM location (spinal column, sacrum, long bones). Bone DCR was defined as the percentage of patients with partial or complete response or stable disease on bone over the study period. DCR was reviewed and confirmed by a medical oncologist and an expert GU radiologist (RLC). The secondary endpoints included bone DCR according to BM number (1, 2-5, >5), and assessment of bone modifications (reconstruction, condensation). All data were exclusively obtained retrospectively, with no procedure taken to recover unavailable data by contacting healthcare providers or patients.
Statistical analysis
Descriptive statistics were utilised to summarise patient demographics, clinical characteristics, and treatment patterns. Categorical variables were expressed as frequency and percentage, and continuous variables as mean and standard deviation or median and range.
Results
Between May 2015 and May 2023, we identified 38 patients with bone metastatic RCC. The median age was 64 years old (range 43-92), and 26 patients (68%) were male. The IMDC score distribution was: 2 favourable (6%), 18 intermediate (47%), and 18 poor (47%) risk patients. Nineteen patients (50%) received an ICI-ICI combination, 17 patients (45%) ICI-TKI and 2 patients (5%) IO alone. Twenty-seven pts (71%) had spinal column metastases, 20 pts (53%) had sacrum metastases and 17 pts (45%) had long bone metastases. Fifteen pts (39%) had 1 BM, 15 pts (39%) had 2-5 BMs and 8 pts (22%) had >5 BMs (Table 1). Sixteen patients (42%) received local treatment of at least one metastatic site. The most frequent was radiotherapy for 6 patients (38%) (Table 1). No patient received specific bone-directed therapy.
Table 1: Patient characteristics
Descriptive statistics were utilised to summarise patient demographics, clinical characteristics, and treatment patterns. Categorical variables were expressed as frequency and percentage, and continuous variables as mean and standard deviation or median and range.
Results
Between May 2015 and May 2023, we identified 38 patients with bone metastatic RCC. The median age was 64 years old (range 43-92), and 26 patients (68%) were male. The IMDC score distribution was: 2 favourable (6%), 18 intermediate (47%), and 18 poor (47%) risk patients. Nineteen patients (50%) received an ICI-ICI combination, 17 patients (45%) ICI-TKI and 2 patients (5%) IO alone. Twenty-seven pts (71%) had spinal column metastases, 20 pts (53%) had sacrum metastases and 17 pts (45%) had long bone metastases. Fifteen pts (39%) had 1 BM, 15 pts (39%) had 2-5 BMs and 8 pts (22%) had >5 BMs (Table 1). Sixteen patients (42%) received local treatment of at least one metastatic site. The most frequent was radiotherapy for 6 patients (38%) (Table 1). No patient received specific bone-directed therapy.
Table 1: Patient characteristics
| Characteristics | Number of patients, n (%) |
| Median age, years (range) | 64 (43-92) |
| Gender | |
| Male Female | 26 (68) 12 (32) |
| IMDC | |
| Favourable Intermediate Unfavorable | 2 (6) 18 (47) 18 (47) |
| Other sites of metastasis | |
| Lymph node Lung Liver | 20 (54) 19 (51) 7 (19) |
| Treatment | |
| ICI + ICI ICI + TKI ICI alone | 19 (50) 17 (45) 2 (5) |
| Local therapy Radiotherapy Interventional radiology Surgery | 16 (42%) 6 (38%) 5 (31%) 4 (25%) |
Overall efficacy
Overall, the DCR for systemic therapy was 68%. Among the 38 patients, 3 patients (8%) achieved a partial response, and 6 patients (16%) achieved a complete response. Nine patients (24%) had progressive disease, and 20 patients (52%) had stable disease as the best response. In total, the ORR was 24%. Regarding the ORR by type of combination, the bone objective response rate was 21% for patients treated with ICI-ICI and 24% for those treated with ICI-TKI.
Efficacy according to BM locations
Out of the 27 patients with spinal column metastases, 4 patients (15%) achieved a CR, 1 patient (4%) had a partial response (PR) and 13 patients (48%) had stable disease (SD). Overall, the DCR was 67% and the ORR was 19%. Out of the 20 patients with sacrum metastases, 3 patients (15%) had a complete response (CR), 2 patients (10%) had a PR and 9 patients (45%) had SD. Overall, the DCR was 70% and the ORR was 25%.
Out of the 17 patients with long bone metastases, 2 patients (12%) had a PR and 10 patients (59%) had SD. Overall, the DCR was 71% and the ORR was 12% (Table 2).
Table 2: Efficacy according to BM sites
Out of the 27 patients with spinal column metastases, 4 patients (15%) achieved a CR, 1 patient (4%) had a partial response (PR) and 13 patients (48%) had stable disease (SD). Overall, the DCR was 67% and the ORR was 19%. Out of the 20 patients with sacrum metastases, 3 patients (15%) had a complete response (CR), 2 patients (10%) had a PR and 9 patients (45%) had SD. Overall, the DCR was 70% and the ORR was 25%.
Out of the 17 patients with long bone metastases, 2 patients (12%) had a PR and 10 patients (59%) had SD. Overall, the DCR was 71% and the ORR was 12% (Table 2).
Table 2: Efficacy according to BM sites
| Spinal column N = 27 | Sacrum N = 20 | Long bones N = 17 | |
| CR, n (%) | 4 (15) | 3 (15) | 0 (0) |
| PR, n (%) | 1 (4) | 2 (10) | 2 (12) |
| SD, n (%) | 13 (48) | 9 (45) | 10 (59) |
| PD, n (%) | 9 (33) | 6 (30) | 5 (29) |
| DCR, n (%) | 18 (67) | 14 (70) | 12 (71) |
Efficacy according to the number of BM
- Out of the 15 patients with 1 BM, 4 patients (27%) achieved a CR, 1 patient (7%) had a PR and 9 patients (59%) had SD. Overall, the DCR was 93%.
- Out of the 15 patients with 2-5 BMs, 2 patients (13%) had a CR, 2 patients (13%) had a PR and 8 patients (53%) had SD. Overall, the DCR was 80%.
- Out of the 8 patients with >5 BMs, 3 patients (37%) had SD as the best response. Overall, the DCR was 37%.
Bone modifications
Eleven patients (29%) developed bone condensation and/or bone reconstruction with a median time to onset of 4.3 months. No patient with bone condensation failed to respond to immunotherapy. With a median follow-up of 45.8 months, only one patient with bone modifications progressed on bone.
Complete responders
A total of 6 patients had a complete bone response. The median age was 57 years (44-75). The IMDC score distribution was: 2 intermediate (33%) and 4 poor (67%) risk patients, respectively. Four patients (67%) received an ICI-ICI combination, 2 patients (33%) IO-TKI. Four patients (67%) had spinal column metastases, and 3 patients (50%) had sacrum metastases. Four patients (67%) had 1 BM, and 2 patients (33%) had 2-5 BMs (Table 3). Three patients (50%) received local treatment for at least one bone metastasis. The median duration of CR was 57 months (8-101). All patients had bone modifications.
Table 3: Complete responder characteristics
Eleven patients (29%) developed bone condensation and/or bone reconstruction with a median time to onset of 4.3 months. No patient with bone condensation failed to respond to immunotherapy. With a median follow-up of 45.8 months, only one patient with bone modifications progressed on bone.
Complete responders
A total of 6 patients had a complete bone response. The median age was 57 years (44-75). The IMDC score distribution was: 2 intermediate (33%) and 4 poor (67%) risk patients, respectively. Four patients (67%) received an ICI-ICI combination, 2 patients (33%) IO-TKI. Four patients (67%) had spinal column metastases, and 3 patients (50%) had sacrum metastases. Four patients (67%) had 1 BM, and 2 patients (33%) had 2-5 BMs (Table 3). Three patients (50%) received local treatment for at least one bone metastasis. The median duration of CR was 57 months (8-101). All patients had bone modifications.
Table 3: Complete responder characteristics
| Characteristics | Number of patients, n (%) |
| Median age, years (range) | 57 (44-75) |
| IMDC | |
| Favourable Intermediate Unfavorable | 0 (0) 2 (33) 4 (67) |
| Sites of bone metastases | |
| Spinal column Sacrum Long bones | 4 (67) 3 (50) 0 (0) |
| Treatment | |
| ICI + ICI ICI + TKI | 4 (67) 3 (33) |
| Local therapy Radiotherapy Interventional radiology Surgery | 3 (50%) 1(17%) 1 (17%) 1 (17%) |
DiscussionBM in RCC
In the present study, we found that bone response in mCRC treated with ICI-based therapy appears to be a response according to RECIST v1.1. BMs occur in approximately one-third of mRCC patients1 and their prevalence is increasing with the advent of new treatments that prolong patients’ outcomes. The presence of BM is associated with poor prognosis, particularly depending on the location and number of BM6. Understanding the efficacy of current treatments for BM in mRCC is crucial for improving patient outcomes.
Immune microenvironment and BM
Understanding the bone immune microenvironment is essential for enhancing the efficacy of tumour immunotherapy. As highlighted by Jiang et al., the immune microenvironment significantly influences the response to immunotherapies. By thoroughly understanding these interactions, we can develop more precise and effective therapeutic strategies, overcoming current challenges related to treatment resistance and variable clinical responses14.
Effectiveness of systemic treatment on BM
During the TKI era, a retrospective study of 188 patients suggested a poor prognosis for patients with BM compared to those without BM. Currently, the first-line treatment for advanced ccRCC is based on anti-PD1 combinations 7–10. The CheckMate 9ER study assessed Nivolumab and Cabozantinib, showing improved overall survival with a hazard ratio (HR) of 0.64 (95% CI 0.39-1.06) in patients with BM 12. Similarly, the CLEAR study demonstrated the benefit of Pembrolizumab and Lenvatinib in first-line treatment, with a sub-group analysis showing improved outcomes for patients with bone metastases 11. In our study, there was no significant difference in the overall response rate between ICI-ICI and ICI-TKI combinations, though the sample size was small.
Specific bone-directed therapy
In our study, no patient received specific bone-directed therapy. BTAs have prospectively shown survival benefits and reduced skeletal-related events (SREs) in several cancer types15–17. However, in mRCC, available data on BTAs are based on retrospective studies from the antiangiogenic TKI era, which reported an increased risk of adverse events, particularly osteonecrosis of the jaw (ONJ), without a benefit on overall survival (OS)18,19. Few data are available in the immunotherapy era. The Phase II NIVOREN study investigating nivolumab and post-antiangiogenic TKI failure suggested that the combination of BTAs with ICI may decrease the incidence of SREs without increasing the risk of ONJ 20.
Bone modifications
Our data suggest that early bone modification seems to correlate with a sustained bone response. Nakata et al. reported in lung cancer that osteosclerotic changes were associated with a favourable prognosis21. This finding highlights the potential importance of early bone response in predicting long-term outcomes.
The main limitations of our study are its single-centre, retrospective design and the small number of patients, which precluded survival analyses.
Conclusion
The bone response in mRCC treated with immune checkpoint inhibitors (ICI) appears to align with RECIST v1.1 criteria and is influenced by the number of bone metastases at baseline. Furthermore, the early appearance of sclerotic bone changes seems to correlate with a favourable bone response. Prospective studies are necessary to confirm these findings and to further elucidate the mechanisms behind bone response in mRCC patients undergoing ICI treatment.
Conflict of interest
Fabien Moinard-Butot certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: F. Moinard-Butot has served in advisory roles for BMS. RL. Cazzato has received travel and accommodation expenses from Medtronic, Ipsen and QUANTUM SURGICAL. L. Pierard has received travel and accommodation expenses from Ipsen, Johnson & Johnson, Pfizer, Eli lilly and company, MUNDI PHARMA. M. Burgy has served in advisory roles for Lilly; reports speaker services for BMS and MSD; has received travel and accommodation expenses from Pfizer, Ipsen and MUNDIPHARMA. G. Malouf has served in advisory roles for BMS, MSD and Ipsen; has received travel and accommodation expenses from MSD, Ipsen and BMS. P. Barthélémy has served in advisory roles for Amgen, Astellas, Bayer, BMS, Ipsen, Janssen Cilag, Merck, MSD, Novartis, Gilead Sciences and Pfizer and reports speaker services for AstraZeneca and Seagen. S. Nannini, M. Pautas, G. Virbel, I. Menoux, C. Schuster, C. Roy, P. Boudier have any conflicts of interest.
Funding
No funding was received for this work.
References
- Woodward E, Jagdev S, McParland L, et al. Skeletal complications and survival in renal cancer patients with bone metastases. Bone. 2011;48(1):160-166. 10.1016/j.bone.2010.09.008
- Kume H, Kakutani S, Yamada Y, et al. Prognostic factors for renal cell carcinoma with bone metastasis: who are the long-term survivors? J Urol. 2011;185(5):1611-1614. 10.1016/j.juro.2010.12.037
- Adiga GU, Dutcher JP, Larkin M, Garl S, Koo J. Characterization of bone metastases in patients with renal cell cancer. BJU Int. 2004;93(9):1237-1240. 10.1111/j.1464-410X.2004.04849.x
- Santoni M, Conti A, Procopio G, et al. Bone metastases in patients with metastatic renal cell carcinoma: are they always associated with poor prognosis? J Exp Clin Cancer Res. 2015;34(1):10. 10.1186/s13046-015-0122-0
- Beuselinck B, Oudard S, Rixe O, et al. Negative impact of bone metastasis on outcome in clear-cell renal cell carcinoma treated with sunitinib. Ann Oncol. 2011;22(4):794-800. 10.1093/annonc/mdq554
- Ruatta F, Derosa L, Escudier B, et al. Prognosis of renal cell carcinoma with bone metastases: Experience from a large cancer centre. Eur J Cancer. 2019;107:79-85. 10.1016/j.ejca.2018.10.023
- Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2018;378(14):1277-1290. 10.1056/NEJMoa1712126
- Motzer R, Alekseev B, Rha SY, et al. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. New England Journal of Medicine. 2021;384(14):1289-1300. 10.1056/NEJMoa2035716
- Choueiri TK, Powles T, Burotto M, et al. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2021;384(9):829-841. 10.1056/NEJMoa2026982
- Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2019;380(12):1116-1127. 10.1056/NEJMoa1816714
- Grünwald V, Powles T, Eto M, et al. Phase 3 CLEAR study in patients with advanced renal cell carcinoma: outcomes in subgroups for the lenvatinib-plus-pembrolizumab and sunitinib arms. Front Oncol. 2023;13:1223282. 10.3389/fonc.2023.1223282
- Apolo A, Powles T, Bourlon MT, et al. Nivolumab plus cabozantinib vs sunitinib in patients with advanced renal cell carcinoma and bone metastasis: subgroup analysis of the phase 3 CheckMate 9ER trial.
- Ko JJ, Xie W, Kroeger N, et al. The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study. Lancet Oncol. 2015;16(3):293-300. 10.1016/S1470-2045(14)71222-7
- Jiang Y, Zhao X, Fu J, Wang H. Progress and Challenges in Precise Treatment of Tumors With PD-1/PD-L1 Blockade. Front Immunol. 2020;11:339. 10.3389/fimmu.2020.00339
- Lipton A, Theriault RL, Hortobagyi GN, et al. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials. Cancer. 2000;88(5):1082-1090. 10.1002/(sici)1097-0142(20000301)88:5<1082::aid-cncr20>3.0.co;2-z
- Isla D, Afonso R, Bosch-Barrera J, Martínez N. Zoledronic acid in lung cancer with bone metastases: a review. Expert Rev Anticancer Ther. 2013;13(4):421-426. 10.1586/era.13.15
- Saad F. Zoledronic acid significantly reduces pathologic fractures in patients with advanced-stage prostate cancer metastatic to bone. Clin Prostate Cancer. 2002;1(3):145-152. 10.3816/cgc.2002.n.016
- Guillot A, Joly C, Barthélémy P, et al. Denosumab Toxicity When Combined With Anti-angiogenic Therapies on Patients With Metastatic Renal Cell Carcinoma: A GETUG Study. Clin Genitourin Cancer. 2019;17(1):e38-e43. 10.1016/j.clgc.2018.08.006
- Omae K, Tsujimoto Y, Honda M, et al. Comparative efficacy and safety of bone-modifying agents for the treatment of bone metastases in patients with advanced renal cell carcinoma: a systematic review and meta-analysis. Oncotarget. 2017;8(40):68890-68898. 10.18632/oncotarget.20323
- Velev M, Dalban C, Chevreau C, et al. Efficacy and safety of nivolumab in bone metastases from renal cell carcinoma: Results of the GETUG-AFU26-NIVOREN multicentre phase II study. Eur J Cancer. 2023;182:66-76. 10.1016/j.ejca.2022.12.028
- Nakata E, Sugihara S, Sugawara Y, et al. Early response of bone metastases can predict tumor response in patients with non-small-cell lung cancer with bone metastases in the treatment with nivolumab. Oncol Lett. 2020;20(3):2977-2986. 10.3892/ol.2020.11856
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In the present study, we found that bone response in mCRC treated with ICI-based therapy appears to be a response according to RECIST v1.1. BMs occur in approximately one-third of mRCC patients1 and their prevalence is increasing with the advent of new treatments that prolong patients’ outcomes. The presence of BM is associated with poor prognosis, particularly depending on the location and number of BM6. Understanding the efficacy of current treatments for BM in mRCC is crucial for improving patient outcomes.
Immune microenvironment and BM
Understanding the bone immune microenvironment is essential for enhancing the efficacy of tumour immunotherapy. As highlighted by Jiang et al., the immune microenvironment significantly influences the response to immunotherapies. By thoroughly understanding these interactions, we can develop more precise and effective therapeutic strategies, overcoming current challenges related to treatment resistance and variable clinical responses14.
Effectiveness of systemic treatment on BM
During the TKI era, a retrospective study of 188 patients suggested a poor prognosis for patients with BM compared to those without BM. Currently, the first-line treatment for advanced ccRCC is based on anti-PD1 combinations 7–10. The CheckMate 9ER study assessed Nivolumab and Cabozantinib, showing improved overall survival with a hazard ratio (HR) of 0.64 (95% CI 0.39-1.06) in patients with BM 12. Similarly, the CLEAR study demonstrated the benefit of Pembrolizumab and Lenvatinib in first-line treatment, with a sub-group analysis showing improved outcomes for patients with bone metastases 11. In our study, there was no significant difference in the overall response rate between ICI-ICI and ICI-TKI combinations, though the sample size was small.
Specific bone-directed therapy
In our study, no patient received specific bone-directed therapy. BTAs have prospectively shown survival benefits and reduced skeletal-related events (SREs) in several cancer types15–17. However, in mRCC, available data on BTAs are based on retrospective studies from the antiangiogenic TKI era, which reported an increased risk of adverse events, particularly osteonecrosis of the jaw (ONJ), without a benefit on overall survival (OS)18,19. Few data are available in the immunotherapy era. The Phase II NIVOREN study investigating nivolumab and post-antiangiogenic TKI failure suggested that the combination of BTAs with ICI may decrease the incidence of SREs without increasing the risk of ONJ 20.
Bone modifications
Our data suggest that early bone modification seems to correlate with a sustained bone response. Nakata et al. reported in lung cancer that osteosclerotic changes were associated with a favourable prognosis21. This finding highlights the potential importance of early bone response in predicting long-term outcomes.
The main limitations of our study are its single-centre, retrospective design and the small number of patients, which precluded survival analyses.
Conclusion
The bone response in mRCC treated with immune checkpoint inhibitors (ICI) appears to align with RECIST v1.1 criteria and is influenced by the number of bone metastases at baseline. Furthermore, the early appearance of sclerotic bone changes seems to correlate with a favourable bone response. Prospective studies are necessary to confirm these findings and to further elucidate the mechanisms behind bone response in mRCC patients undergoing ICI treatment.
Conflict of interest
Fabien Moinard-Butot certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: F. Moinard-Butot has served in advisory roles for BMS. RL. Cazzato has received travel and accommodation expenses from Medtronic, Ipsen and QUANTUM SURGICAL. L. Pierard has received travel and accommodation expenses from Ipsen, Johnson & Johnson, Pfizer, Eli lilly and company, MUNDI PHARMA. M. Burgy has served in advisory roles for Lilly; reports speaker services for BMS and MSD; has received travel and accommodation expenses from Pfizer, Ipsen and MUNDIPHARMA. G. Malouf has served in advisory roles for BMS, MSD and Ipsen; has received travel and accommodation expenses from MSD, Ipsen and BMS. P. Barthélémy has served in advisory roles for Amgen, Astellas, Bayer, BMS, Ipsen, Janssen Cilag, Merck, MSD, Novartis, Gilead Sciences and Pfizer and reports speaker services for AstraZeneca and Seagen. S. Nannini, M. Pautas, G. Virbel, I. Menoux, C. Schuster, C. Roy, P. Boudier have any conflicts of interest.
Funding
No funding was received for this work.
References
- Woodward E, Jagdev S, McParland L, et al. Skeletal complications and survival in renal cancer patients with bone metastases. Bone. 2011;48(1):160-166. 10.1016/j.bone.2010.09.008
- Kume H, Kakutani S, Yamada Y, et al. Prognostic factors for renal cell carcinoma with bone metastasis: who are the long-term survivors? J Urol. 2011;185(5):1611-1614. 10.1016/j.juro.2010.12.037
- Adiga GU, Dutcher JP, Larkin M, Garl S, Koo J. Characterization of bone metastases in patients with renal cell cancer. BJU Int. 2004;93(9):1237-1240. 10.1111/j.1464-410X.2004.04849.x
- Santoni M, Conti A, Procopio G, et al. Bone metastases in patients with metastatic renal cell carcinoma: are they always associated with poor prognosis? J Exp Clin Cancer Res. 2015;34(1):10. 10.1186/s13046-015-0122-0
- Beuselinck B, Oudard S, Rixe O, et al. Negative impact of bone metastasis on outcome in clear-cell renal cell carcinoma treated with sunitinib. Ann Oncol. 2011;22(4):794-800. 10.1093/annonc/mdq554
- Ruatta F, Derosa L, Escudier B, et al. Prognosis of renal cell carcinoma with bone metastases: Experience from a large cancer centre. Eur J Cancer. 2019;107:79-85. 10.1016/j.ejca.2018.10.023
- Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2018;378(14):1277-1290. 10.1056/NEJMoa1712126
- Motzer R, Alekseev B, Rha SY, et al. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. New England Journal of Medicine. 2021;384(14):1289-1300. 10.1056/NEJMoa2035716
- Choueiri TK, Powles T, Burotto M, et al. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2021;384(9):829-841. 10.1056/NEJMoa2026982
- Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2019;380(12):1116-1127. 10.1056/NEJMoa1816714
- Grünwald V, Powles T, Eto M, et al. Phase 3 CLEAR study in patients with advanced renal cell carcinoma: outcomes in subgroups for the lenvatinib-plus-pembrolizumab and sunitinib arms. Front Oncol. 2023;13:1223282. 10.3389/fonc.2023.1223282
- Apolo A, Powles T, Bourlon MT, et al. Nivolumab plus cabozantinib vs sunitinib in patients with advanced renal cell carcinoma and bone metastasis: subgroup analysis of the phase 3 CheckMate 9ER trial.
- Ko JJ, Xie W, Kroeger N, et al. The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study. Lancet Oncol. 2015;16(3):293-300. 10.1016/S1470-2045(14)71222-7
- Jiang Y, Zhao X, Fu J, Wang H. Progress and Challenges in Precise Treatment of Tumors With PD-1/PD-L1 Blockade. Front Immunol. 2020;11:339. 10.3389/fimmu.2020.00339
- Lipton A, Theriault RL, Hortobagyi GN, et al. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials. Cancer. 2000;88(5):1082-1090. 10.1002/(sici)1097-0142(20000301)88:5<1082::aid-cncr20>3.0.co;2-z
- Isla D, Afonso R, Bosch-Barrera J, Martínez N. Zoledronic acid in lung cancer with bone metastases: a review. Expert Rev Anticancer Ther. 2013;13(4):421-426. 10.1586/era.13.15
- Saad F. Zoledronic acid significantly reduces pathologic fractures in patients with advanced-stage prostate cancer metastatic to bone. Clin Prostate Cancer. 2002;1(3):145-152. 10.3816/cgc.2002.n.016
- Guillot A, Joly C, Barthélémy P, et al. Denosumab Toxicity When Combined With Anti-angiogenic Therapies on Patients With Metastatic Renal Cell Carcinoma: A GETUG Study. Clin Genitourin Cancer. 2019;17(1):e38-e43. 10.1016/j.clgc.2018.08.006
- Omae K, Tsujimoto Y, Honda M, et al. Comparative efficacy and safety of bone-modifying agents for the treatment of bone metastases in patients with advanced renal cell carcinoma: a systematic review and meta-analysis. Oncotarget. 2017;8(40):68890-68898. 10.18632/oncotarget.20323
- Velev M, Dalban C, Chevreau C, et al. Efficacy and safety of nivolumab in bone metastases from renal cell carcinoma: Results of the GETUG-AFU26-NIVOREN multicentre phase II study. Eur J Cancer. 2023;182:66-76. 10.1016/j.ejca.2022.12.028
- Nakata E, Sugihara S, Sugawara Y, et al. Early response of bone metastases can predict tumor response in patients with non-small-cell lung cancer with bone metastases in the treatment with nivolumab. Oncol Lett. 2020;20(3):2977-2986. 10.3892/ol.2020.11856
Table of Contents
©2024 the author(s). Published with license by Medicom Medical Publishers.
This an Open Access article distributed under the terms of the Creative Commons attribution-non Commercial license (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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During the TKI era, a retrospective study of 188 patients suggested a poor prognosis for patients with BM compared to those without BM. Currently, the first-line treatment for advanced ccRCC is based on anti-PD1 combinations 7–10. The CheckMate 9ER study assessed Nivolumab and Cabozantinib, showing improved overall survival with a hazard ratio (HR) of 0.64 (95% CI 0.39-1.06) in patients with BM 12. Similarly, the CLEAR study demonstrated the benefit of Pembrolizumab and Lenvatinib in first-line treatment, with a sub-group analysis showing improved outcomes for patients with bone metastases 11. In our study, there was no significant difference in the overall response rate between ICI-ICI and ICI-TKI combinations, though the sample size was small.
Specific bone-directed therapy
In our study, no patient received specific bone-directed therapy. BTAs have prospectively shown survival benefits and reduced skeletal-related events (SREs) in several cancer types15–17. However, in mRCC, available data on BTAs are based on retrospective studies from the antiangiogenic TKI era, which reported an increased risk of adverse events, particularly osteonecrosis of the jaw (ONJ), without a benefit on overall survival (OS)18,19. Few data are available in the immunotherapy era. The Phase II NIVOREN study investigating nivolumab and post-antiangiogenic TKI failure suggested that the combination of BTAs with ICI may decrease the incidence of SREs without increasing the risk of ONJ 20.
Bone modifications
Our data suggest that early bone modification seems to correlate with a sustained bone response. Nakata et al. reported in lung cancer that osteosclerotic changes were associated with a favourable prognosis21. This finding highlights the potential importance of early bone response in predicting long-term outcomes.
The main limitations of our study are its single-centre, retrospective design and the small number of patients, which precluded survival analyses.
Conclusion
The bone response in mRCC treated with immune checkpoint inhibitors (ICI) appears to align with RECIST v1.1 criteria and is influenced by the number of bone metastases at baseline. Furthermore, the early appearance of sclerotic bone changes seems to correlate with a favourable bone response. Prospective studies are necessary to confirm these findings and to further elucidate the mechanisms behind bone response in mRCC patients undergoing ICI treatment.
Conflict of interest
Fabien Moinard-Butot certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: F. Moinard-Butot has served in advisory roles for BMS. RL. Cazzato has received travel and accommodation expenses from Medtronic, Ipsen and QUANTUM SURGICAL. L. Pierard has received travel and accommodation expenses from Ipsen, Johnson & Johnson, Pfizer, Eli lilly and company, MUNDI PHARMA. M. Burgy has served in advisory roles for Lilly; reports speaker services for BMS and MSD; has received travel and accommodation expenses from Pfizer, Ipsen and MUNDIPHARMA. G. Malouf has served in advisory roles for BMS, MSD and Ipsen; has received travel and accommodation expenses from MSD, Ipsen and BMS. P. Barthélémy has served in advisory roles for Amgen, Astellas, Bayer, BMS, Ipsen, Janssen Cilag, Merck, MSD, Novartis, Gilead Sciences and Pfizer and reports speaker services for AstraZeneca and Seagen. S. Nannini, M. Pautas, G. Virbel, I. Menoux, C. Schuster, C. Roy, P. Boudier have any conflicts of interest.
Funding
No funding was received for this work.
References
- Woodward E, Jagdev S, McParland L, et al. Skeletal complications and survival in renal cancer patients with bone metastases. Bone. 2011;48(1):160-166. 10.1016/j.bone.2010.09.008
- Kume H, Kakutani S, Yamada Y, et al. Prognostic factors for renal cell carcinoma with bone metastasis: who are the long-term survivors? J Urol. 2011;185(5):1611-1614. 10.1016/j.juro.2010.12.037
- Adiga GU, Dutcher JP, Larkin M, Garl S, Koo J. Characterization of bone metastases in patients with renal cell cancer. BJU Int. 2004;93(9):1237-1240. 10.1111/j.1464-410X.2004.04849.x
- Santoni M, Conti A, Procopio G, et al. Bone metastases in patients with metastatic renal cell carcinoma: are they always associated with poor prognosis? J Exp Clin Cancer Res. 2015;34(1):10. 10.1186/s13046-015-0122-0
- Beuselinck B, Oudard S, Rixe O, et al. Negative impact of bone metastasis on outcome in clear-cell renal cell carcinoma treated with sunitinib. Ann Oncol. 2011;22(4):794-800. 10.1093/annonc/mdq554
- Ruatta F, Derosa L, Escudier B, et al. Prognosis of renal cell carcinoma with bone metastases: Experience from a large cancer centre. Eur J Cancer. 2019;107:79-85. 10.1016/j.ejca.2018.10.023
- Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2018;378(14):1277-1290. 10.1056/NEJMoa1712126
- Motzer R, Alekseev B, Rha SY, et al. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. New England Journal of Medicine. 2021;384(14):1289-1300. 10.1056/NEJMoa2035716
- Choueiri TK, Powles T, Burotto M, et al. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2021;384(9):829-841. 10.1056/NEJMoa2026982
- Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2019;380(12):1116-1127. 10.1056/NEJMoa1816714
- Grünwald V, Powles T, Eto M, et al. Phase 3 CLEAR study in patients with advanced renal cell carcinoma: outcomes in subgroups for the lenvatinib-plus-pembrolizumab and sunitinib arms. Front Oncol. 2023;13:1223282. 10.3389/fonc.2023.1223282
- Apolo A, Powles T, Bourlon MT, et al. Nivolumab plus cabozantinib vs sunitinib in patients with advanced renal cell carcinoma and bone metastasis: subgroup analysis of the phase 3 CheckMate 9ER trial.
- Ko JJ, Xie W, Kroeger N, et al. The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study. Lancet Oncol. 2015;16(3):293-300. 10.1016/S1470-2045(14)71222-7
- Jiang Y, Zhao X, Fu J, Wang H. Progress and Challenges in Precise Treatment of Tumors With PD-1/PD-L1 Blockade. Front Immunol. 2020;11:339. 10.3389/fimmu.2020.00339
- Lipton A, Theriault RL, Hortobagyi GN, et al. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials. Cancer. 2000;88(5):1082-1090. 10.1002/(sici)1097-0142(20000301)88:5<1082::aid-cncr20>3.0.co;2-z
- Isla D, Afonso R, Bosch-Barrera J, Martínez N. Zoledronic acid in lung cancer with bone metastases: a review. Expert Rev Anticancer Ther. 2013;13(4):421-426. 10.1586/era.13.15
- Saad F. Zoledronic acid significantly reduces pathologic fractures in patients with advanced-stage prostate cancer metastatic to bone. Clin Prostate Cancer. 2002;1(3):145-152. 10.3816/cgc.2002.n.016
- Guillot A, Joly C, Barthélémy P, et al. Denosumab Toxicity When Combined With Anti-angiogenic Therapies on Patients With Metastatic Renal Cell Carcinoma: A GETUG Study. Clin Genitourin Cancer. 2019;17(1):e38-e43. 10.1016/j.clgc.2018.08.006
- Omae K, Tsujimoto Y, Honda M, et al. Comparative efficacy and safety of bone-modifying agents for the treatment of bone metastases in patients with advanced renal cell carcinoma: a systematic review and meta-analysis. Oncotarget. 2017;8(40):68890-68898. 10.18632/oncotarget.20323
- Velev M, Dalban C, Chevreau C, et al. Efficacy and safety of nivolumab in bone metastases from renal cell carcinoma: Results of the GETUG-AFU26-NIVOREN multicentre phase II study. Eur J Cancer. 2023;182:66-76. 10.1016/j.ejca.2022.12.028
- Nakata E, Sugihara S, Sugawara Y, et al. Early response of bone metastases can predict tumor response in patients with non-small-cell lung cancer with bone metastases in the treatment with nivolumab. Oncol Lett. 2020;20(3):2977-2986. 10.3892/ol.2020.11856
Table of Contents
©2024 the author(s). Published with license by Medicom Medical Publishers.
This an Open Access article distributed under the terms of the Creative Commons attribution-non Commercial license (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Posted on
site created by:
© 2024 Medicom Medical Publishers. All rights reserved.
Terms and Conditions
| Privacy Policy
HEAD OFFICE
Laarderhoogtweg 25
1101 EB Amsterdam
The Netherlands
T: +31 85 4012 560
E: publishers@medicom-publishers.com
Our data suggest that early bone modification seems to correlate with a sustained bone response. Nakata et al. reported in lung cancer that osteosclerotic changes were associated with a favourable prognosis21. This finding highlights the potential importance of early bone response in predicting long-term outcomes.
The main limitations of our study are its single-centre, retrospective design and the small number of patients, which precluded survival analyses.
Conclusion
The bone response in mRCC treated with immune checkpoint inhibitors (ICI) appears to align with RECIST v1.1 criteria and is influenced by the number of bone metastases at baseline. Furthermore, the early appearance of sclerotic bone changes seems to correlate with a favourable bone response. Prospective studies are necessary to confirm these findings and to further elucidate the mechanisms behind bone response in mRCC patients undergoing ICI treatment.
Conflict of interest
Fabien Moinard-Butot certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: F. Moinard-Butot has served in advisory roles for BMS. RL. Cazzato has received travel and accommodation expenses from Medtronic, Ipsen and QUANTUM SURGICAL. L. Pierard has received travel and accommodation expenses from Ipsen, Johnson & Johnson, Pfizer, Eli lilly and company, MUNDI PHARMA. M. Burgy has served in advisory roles for Lilly; reports speaker services for BMS and MSD; has received travel and accommodation expenses from Pfizer, Ipsen and MUNDIPHARMA. G. Malouf has served in advisory roles for BMS, MSD and Ipsen; has received travel and accommodation expenses from MSD, Ipsen and BMS. P. Barthélémy has served in advisory roles for Amgen, Astellas, Bayer, BMS, Ipsen, Janssen Cilag, Merck, MSD, Novartis, Gilead Sciences and Pfizer and reports speaker services for AstraZeneca and Seagen. S. Nannini, M. Pautas, G. Virbel, I. Menoux, C. Schuster, C. Roy, P. Boudier have any conflicts of interest.
Funding
No funding was received for this work.
References
- Woodward E, Jagdev S, McParland L, et al. Skeletal complications and survival in renal cancer patients with bone metastases. Bone. 2011;48(1):160-166. 10.1016/j.bone.2010.09.008
- Kume H, Kakutani S, Yamada Y, et al. Prognostic factors for renal cell carcinoma with bone metastasis: who are the long-term survivors? J Urol. 2011;185(5):1611-1614. 10.1016/j.juro.2010.12.037
- Adiga GU, Dutcher JP, Larkin M, Garl S, Koo J. Characterization of bone metastases in patients with renal cell cancer. BJU Int. 2004;93(9):1237-1240. 10.1111/j.1464-410X.2004.04849.x
- Santoni M, Conti A, Procopio G, et al. Bone metastases in patients with metastatic renal cell carcinoma: are they always associated with poor prognosis? J Exp Clin Cancer Res. 2015;34(1):10. 10.1186/s13046-015-0122-0
- Beuselinck B, Oudard S, Rixe O, et al. Negative impact of bone metastasis on outcome in clear-cell renal cell carcinoma treated with sunitinib. Ann Oncol. 2011;22(4):794-800. 10.1093/annonc/mdq554
- Ruatta F, Derosa L, Escudier B, et al. Prognosis of renal cell carcinoma with bone metastases: Experience from a large cancer centre. Eur J Cancer. 2019;107:79-85. 10.1016/j.ejca.2018.10.023
- Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2018;378(14):1277-1290. 10.1056/NEJMoa1712126
- Motzer R, Alekseev B, Rha SY, et al. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. New England Journal of Medicine. 2021;384(14):1289-1300. 10.1056/NEJMoa2035716
- Choueiri TK, Powles T, Burotto M, et al. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2021;384(9):829-841. 10.1056/NEJMoa2026982
- Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2019;380(12):1116-1127. 10.1056/NEJMoa1816714
- Grünwald V, Powles T, Eto M, et al. Phase 3 CLEAR study in patients with advanced renal cell carcinoma: outcomes in subgroups for the lenvatinib-plus-pembrolizumab and sunitinib arms. Front Oncol. 2023;13:1223282. 10.3389/fonc.2023.1223282
- Apolo A, Powles T, Bourlon MT, et al. Nivolumab plus cabozantinib vs sunitinib in patients with advanced renal cell carcinoma and bone metastasis: subgroup analysis of the phase 3 CheckMate 9ER trial.
- Ko JJ, Xie W, Kroeger N, et al. The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study. Lancet Oncol. 2015;16(3):293-300. 10.1016/S1470-2045(14)71222-7
- Jiang Y, Zhao X, Fu J, Wang H. Progress and Challenges in Precise Treatment of Tumors With PD-1/PD-L1 Blockade. Front Immunol. 2020;11:339. 10.3389/fimmu.2020.00339
- Lipton A, Theriault RL, Hortobagyi GN, et al. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials. Cancer. 2000;88(5):1082-1090. 10.1002/(sici)1097-0142(20000301)88:5<1082::aid-cncr20>3.0.co;2-z
- Isla D, Afonso R, Bosch-Barrera J, Martínez N. Zoledronic acid in lung cancer with bone metastases: a review. Expert Rev Anticancer Ther. 2013;13(4):421-426. 10.1586/era.13.15
- Saad F. Zoledronic acid significantly reduces pathologic fractures in patients with advanced-stage prostate cancer metastatic to bone. Clin Prostate Cancer. 2002;1(3):145-152. 10.3816/cgc.2002.n.016
- Guillot A, Joly C, Barthélémy P, et al. Denosumab Toxicity When Combined With Anti-angiogenic Therapies on Patients With Metastatic Renal Cell Carcinoma: A GETUG Study. Clin Genitourin Cancer. 2019;17(1):e38-e43. 10.1016/j.clgc.2018.08.006
- Omae K, Tsujimoto Y, Honda M, et al. Comparative efficacy and safety of bone-modifying agents for the treatment of bone metastases in patients with advanced renal cell carcinoma: a systematic review and meta-analysis. Oncotarget. 2017;8(40):68890-68898. 10.18632/oncotarget.20323
- Velev M, Dalban C, Chevreau C, et al. Efficacy and safety of nivolumab in bone metastases from renal cell carcinoma: Results of the GETUG-AFU26-NIVOREN multicentre phase II study. Eur J Cancer. 2023;182:66-76. 10.1016/j.ejca.2022.12.028
- Nakata E, Sugihara S, Sugawara Y, et al. Early response of bone metastases can predict tumor response in patients with non-small-cell lung cancer with bone metastases in the treatment with nivolumab. Oncol Lett. 2020;20(3):2977-2986. 10.3892/ol.2020.11856
Table of Contents
©2024 the author(s). Published with license by Medicom Medical Publishers.
This an Open Access article distributed under the terms of the Creative Commons attribution-non Commercial license (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Posted on
site created by:
© 2024 Medicom Medical Publishers. All rights reserved.
Terms and Conditions
| Privacy Policy
HEAD OFFICE
Laarderhoogtweg 25
1101 EB Amsterdam
The Netherlands
T: +31 85 4012 560
E: publishers@medicom-publishers.com
Fabien Moinard-Butot certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: F. Moinard-Butot has served in advisory roles for BMS. RL. Cazzato has received travel and accommodation expenses from Medtronic, Ipsen and QUANTUM SURGICAL. L. Pierard has received travel and accommodation expenses from Ipsen, Johnson & Johnson, Pfizer, Eli lilly and company, MUNDI PHARMA. M. Burgy has served in advisory roles for Lilly; reports speaker services for BMS and MSD; has received travel and accommodation expenses from Pfizer, Ipsen and MUNDIPHARMA. G. Malouf has served in advisory roles for BMS, MSD and Ipsen; has received travel and accommodation expenses from MSD, Ipsen and BMS. P. Barthélémy has served in advisory roles for Amgen, Astellas, Bayer, BMS, Ipsen, Janssen Cilag, Merck, MSD, Novartis, Gilead Sciences and Pfizer and reports speaker services for AstraZeneca and Seagen. S. Nannini, M. Pautas, G. Virbel, I. Menoux, C. Schuster, C. Roy, P. Boudier have any conflicts of interest.
Funding
No funding was received for this work.
References
- Woodward E, Jagdev S, McParland L, et al. Skeletal complications and survival in renal cancer patients with bone metastases. Bone. 2011;48(1):160-166. 10.1016/j.bone.2010.09.008
- Kume H, Kakutani S, Yamada Y, et al. Prognostic factors for renal cell carcinoma with bone metastasis: who are the long-term survivors? J Urol. 2011;185(5):1611-1614. 10.1016/j.juro.2010.12.037
- Adiga GU, Dutcher JP, Larkin M, Garl S, Koo J. Characterization of bone metastases in patients with renal cell cancer. BJU Int. 2004;93(9):1237-1240. 10.1111/j.1464-410X.2004.04849.x
- Santoni M, Conti A, Procopio G, et al. Bone metastases in patients with metastatic renal cell carcinoma: are they always associated with poor prognosis? J Exp Clin Cancer Res. 2015;34(1):10. 10.1186/s13046-015-0122-0
- Beuselinck B, Oudard S, Rixe O, et al. Negative impact of bone metastasis on outcome in clear-cell renal cell carcinoma treated with sunitinib. Ann Oncol. 2011;22(4):794-800. 10.1093/annonc/mdq554
- Ruatta F, Derosa L, Escudier B, et al. Prognosis of renal cell carcinoma with bone metastases: Experience from a large cancer centre. Eur J Cancer. 2019;107:79-85. 10.1016/j.ejca.2018.10.023
- Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2018;378(14):1277-1290. 10.1056/NEJMoa1712126
- Motzer R, Alekseev B, Rha SY, et al. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. New England Journal of Medicine. 2021;384(14):1289-1300. 10.1056/NEJMoa2035716
- Choueiri TK, Powles T, Burotto M, et al. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2021;384(9):829-841. 10.1056/NEJMoa2026982
- Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2019;380(12):1116-1127. 10.1056/NEJMoa1816714
- Grünwald V, Powles T, Eto M, et al. Phase 3 CLEAR study in patients with advanced renal cell carcinoma: outcomes in subgroups for the lenvatinib-plus-pembrolizumab and sunitinib arms. Front Oncol. 2023;13:1223282. 10.3389/fonc.2023.1223282
- Apolo A, Powles T, Bourlon MT, et al. Nivolumab plus cabozantinib vs sunitinib in patients with advanced renal cell carcinoma and bone metastasis: subgroup analysis of the phase 3 CheckMate 9ER trial.
- Ko JJ, Xie W, Kroeger N, et al. The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study. Lancet Oncol. 2015;16(3):293-300. 10.1016/S1470-2045(14)71222-7
- Jiang Y, Zhao X, Fu J, Wang H. Progress and Challenges in Precise Treatment of Tumors With PD-1/PD-L1 Blockade. Front Immunol. 2020;11:339. 10.3389/fimmu.2020.00339
- Lipton A, Theriault RL, Hortobagyi GN, et al. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials. Cancer. 2000;88(5):1082-1090. 10.1002/(sici)1097-0142(20000301)88:5<1082::aid-cncr20>3.0.co;2-z
- Isla D, Afonso R, Bosch-Barrera J, Martínez N. Zoledronic acid in lung cancer with bone metastases: a review. Expert Rev Anticancer Ther. 2013;13(4):421-426. 10.1586/era.13.15
- Saad F. Zoledronic acid significantly reduces pathologic fractures in patients with advanced-stage prostate cancer metastatic to bone. Clin Prostate Cancer. 2002;1(3):145-152. 10.3816/cgc.2002.n.016
- Guillot A, Joly C, Barthélémy P, et al. Denosumab Toxicity When Combined With Anti-angiogenic Therapies on Patients With Metastatic Renal Cell Carcinoma: A GETUG Study. Clin Genitourin Cancer. 2019;17(1):e38-e43. 10.1016/j.clgc.2018.08.006
- Omae K, Tsujimoto Y, Honda M, et al. Comparative efficacy and safety of bone-modifying agents for the treatment of bone metastases in patients with advanced renal cell carcinoma: a systematic review and meta-analysis. Oncotarget. 2017;8(40):68890-68898. 10.18632/oncotarget.20323
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- Omae K, Tsujimoto Y, Honda M, et al. Comparative efficacy and safety of bone-modifying agents for the treatment of bone metastases in patients with advanced renal cell carcinoma: a systematic review and meta-analysis. Oncotarget. 2017;8(40):68890-68898. 10.18632/oncotarget.20323
- Velev M, Dalban C, Chevreau C, et al. Efficacy and safety of nivolumab in bone metastases from renal cell carcinoma: Results of the GETUG-AFU26-NIVOREN multicentre phase II study. Eur J Cancer. 2023;182:66-76. 10.1016/j.ejca.2022.12.028
- Nakata E, Sugihara S, Sugawara Y, et al. Early response of bone metastases can predict tumor response in patients with non-small-cell lung cancer with bone metastases in the treatment with nivolumab. Oncol Lett. 2020;20(3):2977-2986. 10.3892/ol.2020.11856
Table of Contents
©2024 the author(s). Published with license by Medicom Medical Publishers.
This an Open Access article distributed under the terms of the Creative Commons attribution-non Commercial license (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Posted on
site created by:
© 2024 Medicom Medical Publishers. All rights reserved. Terms and Conditions | Privacy Policy
HEAD OFFICE
Laarderhoogtweg 25
1101 EB Amsterdam
The Netherlands
T: +31 85 4012 560
E: publishers@medicom-publishers.com