Second-line treatment with tumour-infiltrating lymphocytes (TIL) improved progression-free survival (PFS) compared with ipilimumab in patients with advanced, non-resectable stage III–IV melanoma, the results from an investigator-driven randomised phase 3 trial showed.
Although immune checkpoint inhibitors and targeted therapies have profoundly improved the outcome of patients with (advanced) melanoma, approximately 50% of patients still die from their disease within 5 years following diagnosis of stage IV disease . Adoptive cell therapy with TIL is an (elaborative and time-consuming) treatment modality with promising response rates of 36–70% in heavily pre-treated patients with advanced melanoma, observed in multiple phase 1/2 trials [2,3]. Prof. John Haanen (Netherlands Cancer Institute, the Netherlands) and colleagues performed the first investigator-driven, open-label, randomised-controlled, phase 3 clinical trial (NCT02278887) comparing treatments with TIL and ipilimumab .
In this trial, 168 patients with unresectable, stage III–IV cutaneous melanoma who had progression after 1 line of systemic treatment (no ipilimumab) were randomised to receive TIL treatment (single infusion of ≥5×109 TILs) or ipilimumab (3 mg/kg every 3 weeks, max. 4 doses). About 90% of the participants had received prior anti-PD1 therapy. The primary endpoint of the study was PFS in the intention-to-treat (ITT) population; secondary endpoints were overall and complete response rate (RR), overall survival (OS), and safety.
The trial met its endpoint: with a median follow-up of 33 months, the median PFS was 7.2 months for the participants randomised to TIL treatment versus 2.1 months for the patients treated with ipilimumab (HR 0.50; P<0.001). PFS rates at 6 months were 52.7% and 21.4% (TIL vs ipilimumab, respectively). ORR was 48.8% in the TIL-receiving participants (20.2% complete response) compared with 21.4% in the ipilimumab-treated participants (7.1% complete response). Preliminary OS data showed a trend in favour of TIL treatment; the median OS was 25.8 months in the TIL-receiving participants versus 18.9 months in participants on ipilimumab (HR 0.83; P=0.39). The safety of TIL treatment was manageable and scores for health-related quality-of-life were significantly higher in TIL-treated participants during the 60 months of follow-up (Δmean at 6 months 7.7; P<0.01) than in the ipilimumab-treated group.
“This first randomised phase 3 trial demonstrates that second-line TIL administration significantly improves PFS compared with ipilimumab in patients with unresectable, advanced melanoma. Therefore, TIL therapy could become a possible new treatment option for this population,” highlighted Prof. Haanen.
- Larkin J, et al. N Engl J Med. 2019;381(16):1535–1546.
- Van den Berg JH, et al. J Immunother Cancer. 2020;8(2):e000848.
- Sarnaik AA, et al. J Clin Oncol. 2021;39(24):2656–2666.
- Haanen JBAG, et al. Treatment with tumor-infiltrating lymphocytes (TIL) versus ipilimumab for advanced melanoma: Results from a multicenter, randomized phase III trial. Abstract LBA3, ESMO Congress 2022, 09–13 September, Paris, France.
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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