PD-L1 expression and response to immunotherapy in patients with MET exon 14-altered non-small cell lung cancers (NSCLC).

Abstract

8512 Background: MET exon 14 skipping alterations ( METΔ14) are present in 4% of NSCLCs. Response to MET inhibition has been observed in ongoing prospective trials (44% response rate, phase 1 trial of crizotinib; Drilon et al ASCO 2016), however responses to other types or therapy, such as immunotherapy, is unknown. We evaluated the immunophenotype of METΔ14 lung cancers and response to PD-(L)-1-based immunotherapy. Methods: Pts with recurrent/metastatic NSCLC were eligible. METΔ14 was identified by broad hybrid capture-based next-generation sequencing (MSK-IMPACT). PD-L1 expression was determined by immunohistochemistry. Response to immune therapy was evaluated by RECIST v1.1. Results: 63 pts with METΔ14-positive non-small cell lung cancers were identified; 41 (65%) had sufficient tissue for PD-L1 analysis. Patient characteristics: median age 71 years, 58% female, median pack year smoking 5.85 years, histology: 73% (30/41) adenocarcinoma, 20% (8/41) pleomorphic carcinoma, 7% (3/41) squamous cell. Tumor PD-L1 expression was ≥50% in 44% (18/41, 95% CI 30-59%), 1-49% in 17% (7/41, 95% CI 8-32%), and < 1 in 39% (16/41, 95% CI 26-54%). The median age for patients with METΔ14 and PD-L1 positive (≥1%) tumors was 65 years (range 49-87); 60% (15/25) of patients were female; Histology: 72% (18/25) adenocarcinoma, 24% (6/25) sarcomatoid carcinoma, and 4% (1/25) squamous cell carcinoma. Immunotherapy was given to 15 pts: nivolumab (5), pembrolizumab (3), atezolizumab (2), durvalumab (1), and ipilimumab+nivolumab (4). The overall response rate to immunotherapy was 13% (2/15, 95% CI 3-39%). Overall response was 33% (1/3; 95% CI 6-80%) in patients with tumors PD-L1 ≥50%, and 20% (1/5, 95%CI 2-64%) in patients with tumors PD-L1 0%. Time on therapy ranged from 2 weeks to 9.6+ months. Conclusions: A substantial proportion of NSCLCs harboring METΔ14 alterations express PD-L1. Despite frequent PD-L1 expression, responses to immunotherapy were overall uncommon and lower than that observed with targeted therapy for this genomically defined subset of patients with lung cancers. Further exploration of this subset may reveal important mechanisms of immunotherapy resistance in PD-L1 expressing tumors.