PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers Journal Article
| Authors: | Sabari, J. K.; Leonardi, G. C.; Shu, C. A.; Umeton, R.; Montecalvo, J.; Ni, A.; Chen, R.; Dienstag, J.; Mrad, C.; Bergagnini, I.; Lai, W. V.; Offin, M.; Arbour, K. C.; Plodkowski, A. J.; Halpenny, D. F.; Paik, P. K.; Li, B. T.; Riely, G. J.; Kris, M. G.; Rudin, C. M.; Sholl, L. M.; Nishino, M.; Hellmann, M. D.; Rekhtman, N.; Awad, M. M.; Drilon, A. |
| Article Title: | PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers |
| Abstract: | Background: MET exon 14 alterations are actionable oncogenic drivers. Durable responses to MET inhibitors are observed in patients with advanced MET exon 14-altered lung cancers in prospective trials. In contrast, the activity of immunotherapy, PD-L1 expression and tumor mutational burden (TMB) of these tumors and are not well characterized. Patients and methods: Patients with MET exon 14-altered lung cancers of any stage treated at two academic institutions were identified. A review of clinicopathologic and molecular features, and an analysis of response to single-agent or combination immune checkpoint inhibition were conducted. PD-L1 immunohistochemistry was carried out and TMB was calculated by estimation from targeted next-generation sequencing panels. Results: We identified 147 patients with MET exon 14-altered lung cancers. PD-L1 expression of 0%, 1%-49%, and ≥50% were 37%, 22%, and 41%, respectively, in 111 evaluable tumor samples. The median TMB of MET exon 14-altered lung cancers was lower than that of unselected non-small-cell lung cancers (NSCLCs) in both independently evaluated cohorts: 3.8 versus 5.7 mutations/megabase (P < 0.001, n = 78 versus 1769, cohort A), and 7.3 versus 11.8 mutations/megabase (P < 0.001, n = 62 versus 1100, cohort B). There was no association between PD-L1 expression and TMB (Spearman's rho=0.18, P = 0.069). In response-evaluable patients (n = 24), the objective response rate was 17% (95% CI 6% to 36%) and the median progression-free survival was 1.9 months (95% CI 1.7-2.7). Responses were not enriched in tumors with PD-L1 expression ≥50% nor high TMB. Conclusion: A substantial proportion of MET exon 14-altered lung cancers express PD-L1, but the median TMB is lower compared with unselected NSCLCs. Occasional responses to PD-1 blockade can be achieved, but overall clinical efficacy is modest. |
| Journal Title: | Annals of Oncology |
| Volume: | 29 |
| Issue: | 10 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2018-10-01 |
| Start Page: | 2085 |
| End Page: | 2091 |
| Language: | English |
| DOI: | 10.1093/annonc/mdy334 |
| PUBMED: | 30165371 |
| PROVIDER: | scopus |
| PMCID: | PMC6225900 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 December 2018 -- Source: Scopus |
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