K. Loo1,2, I. Soliman2, J. D’Souza2, M. Renzetti1,2, T. Li2, H. Wu2, B. Luo2, S. Movva2, M. Lango2, A. Olszanski2, J. Farma2 1Temple University,Surgical Oncology,Philadelpha, PA, USA 2Fox Chase Cancer Center,Surgical Oncology,Philadelphia, PA, USA
Introduction: Considerable advances in melanoma therapy have been realized through immunotherapy. Unfortunately, there remains a subset of patients who fail to respond. There is a need to identify patients likely to exhibit sustained response to immunotherapy agents, versus those who would benefit from alternate therapies. It remains to be seen whether a patient’s tumor molecular gene profile could serve as a marker of response. The principle aim of this study was to utilize molecular profiling to determine the difference in gene mutation status between responders and non-responders prior to initial immunotherapy.
Methods: Tissue samples from n=42 melanoma patients were collected. Pre-treatment tumors were profiled using a Next Generation Sequencing (NGS) panel of 50 targetable cancer-related gene mutations. Gene mutation status was analyzed. Response to immunotherapy was assessed using RECIST v1.1 criteria. Statistical analysis was conducted using Fisher’s exact test.
Results: Within the total cohort, patients received initial immunotherapy of anti-CTLA4 (n=7), anti-PD1 (n=22), ipilimumab/nivolumab combination (n=7), or clinical trial immunotherapy combinations (n=7), and were divided into responders (n=17) or non-responders (n=25). 62% were male, with a median age of 68. 65 total mutations were identified affecting 36 unique genes. No mutations were found in 10% of patients, while 52% had 1 mutation, 28% had 2 mutations, 5% had 3 mutations, and 5% had 4 or more mutations. The overall hot-spot mutation burden in the responder cohort was 1.80 versus 1.32 in the non-responder cohort. The most common mutation among responders was NRAS, detected in 70.5% of responders, vs 29.4% in non-responders. Additionally, the most common mutation among non-responders was a BRAF mutation, identified in 18.2% of responders vs. in 81.8% of non-responders.
Conclusion: Using our NGS platform, this analysis demonstrated potential associations between NRAS mutation and responders to immunotherapy, and correlations between BRAF mutation and non-responders. This unique finding should be evaluated in a larger population to confirm these results and may help predict response in the future.