Avelumab administration in the second line improved progression-free survival (PFS) in patients with microsatellite instability-high (MSI-H)/ DNA mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) who are naïve to immune checkpoint inhibition, results from the SAMCO-PRODIGE 54 trial demonstrated.
MSI-high/dMMR colorectal tumours are currently the only colorectal tumours sensitive to immune checkpoint inhibition with pembrolizumab improving PFS in the first-line setting [1,2]. The phase 2 SAMCO-PRODIGE 54 trial (NCT03186326), presented by Prof. Julien Taieb (Hopital European George Pompidou, France), evaluated the efficacy of avelumab in the second-line for patients with MSI-high/dMMR mCRC versus standard-of-care .
The open-label, phase 2 trial randomised 122 patients with MSI-high/dMMR mCRC who progressed on oxaliplatin- or irinotecan-based first-line therapy (and targeted agents if indicated) to avelumab (10 mg/kg every 2 weeks) or standard second-line chemotherapy. The primary endpoint was PFS.
Due to Kaplan-Meier PFS curves crossing at 7.3 months, the log-rank test and HR assessment of treatment were invalid. Instead, the 2-stage procedure according to Qiu and Sheng was performed . Second-line avelumab improved PFS significantly versus standard-of-care (P=0.025). PFS rates were 31% versus 19% at 12 months, 27% versus 9% at 18 months, and 25% versus 3% at 24 months for avelumab and standard-of-care, respectively. Objective response rates and disease control rates were similar between the treatment arms; however, disease control was maintained for 18 months with avelumab in most patients. Treatment with avelumab led to lower rates of grade ≥3 adverse events.
“This trial demonstrated that avelumab is safe and effective when used in the second-line in patients with MSI-high/dMMR mCRC, confirming that immune checkpoint inhibition remains relevant beyond first-line in patients naïve to immune checkpoint inhibition. However, the indirect comparison suggests that these patients should be treated with immune checkpoint inhibitors as soon as possible,” stated Prof. Taieb. Indeed, the phase 3 KEYNOTE-177 trial confirms the effects of first-line pembrolizumab for this population of MSI-H CRC.
- Eng C, et al. Lancet Oncol. 2019;20(6)849–861.
- André T, et al. N Engl J Med. 2020;383(23);2207–2218.
- Taieb J, et al. Avelumab versus standard second-line treatment chemotherapy in metastatic colorectal cancer (mCRC) patients with microsatellite instability (MSI): The SAMCO-PRODIGE 54 randomised phase II trial. Abstract LBA23, ESMO Congress 2022, 09–13 September Paris, France.
- Qiu P, Sheng J. J R Stat Soc Ser B Stat Methodol. 2008;70:191–208.
- André T, et al. N Engl J Med. 2020;383(23):2207-2218.
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Table of Contents: ESMO 2022
Letter from the Editor
High pathological responses to neoadjuvant immune checkpoint inhibition in locally advanced dMMR colon cancer
Fruquintinib: a potential new treatment for patients with refractory mCRC
Second-line avelumab is effective in patients with MSI-H/dMMR mCRC
Upper Gastrointestinal Cancer
Deep learning models predict the risk of relapse and the mutational profile in GIST
Addition of pembrolizumab to lenvatinib does not improve OS in advanced HCC
New, highly selective inhibitor of FGFR2 driver alterations and resistance mutations
Chemo-immunotherapy in gastric cancer is more effective when administered in parallel
Tumour infiltrating lymphocytes identify patients with immunogenic triple-negative breast cancer
OS benefit of abemaciclib in HR-positive/HER2-negative advanced breast cancer not (yet) statistically significant
OS benefit of sacituzumab govitecan in pre-treated HR-positive/HER2-negative metastatic breast cancer
A pathway from air pollution to lung cancer in non-smokers identified
Selective KRASG12C inhibitor sotorasib demonstrates superior PFS and ORR compared to docetaxel in previously treated patients with NSCLC
Promising clinical activity of tepotinib plus osimertinib in NSCLC with MET amplification after progression on first-line osimertinib
High pathological responses in borderline resectable NSCLC patients after induction with dual immunotherapy and concurrent chemoradiotherapy
Treatment with tumour-infiltrating lymphocytes for advanced melanoma outperforms ipilimumab
Neoadjuvant pembrolizumab outperforms adjuvant pembrolizumab in resectable stage III–IV melanomas
Survival-benefit of neoadjuvant T-VEC maintained over 5 years of follow-up
Baseline ctDNA predicts survival in resected stage III–IV melanoma
Genitourinary Cancer – Prostate Cancer
Overall survival benefit of abiraterone in mHSPC is maintained for 7 years
Limited benefit of adding long-term ADT to post-operative radiotherapy in prostate cancer
Intensified ADT benefits biochemical progression-free survival in biochemically relapsed prostate cancer
Genitourinary Cancer – Non-Prostate Cancer
Adjuvant nivolumab plus ipilimumab does not improve survival in patients with localised RCC at high risk of relapse after nephrectomy
Triple therapy improves progression-free survival in patients with advanced RCC versus dual therapy
Adjuvant atezolizumab does not improve outcomes for patients with RCC and increased risk of recurrence
OS benefit for advanced ovarian cancer patients treated with maintenance olaparib
Maintenance tegafur-uracil does not improve survival in locally advanced cervical cancer
Head and Neck Cancer
Adding first-line pembrolizumab to CRT in locally advanced HNSCC does not significantly prolong survival or event-free survival
5-FU-free chemotherapy combination as an alternative for first-line treatment of recurrent or metastatic HNSCC
Epstein Barr virus-specific autologous cytotoxic T lymphocytes do not improve survival in nasopharyngeal carcinoma