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
Notes: Article -- Export Date: 3 December 2018 -- Source: Scopus
Citation Impact
MSK Authors
  1. Gregory J Riely
    421 Riely
  2. Paul K Paik
    112 Paik
  3. Mark Kris
    718 Kris
  4. Alexander Edward Drilon
    251 Drilon
  5. Matthew David Hellmann
    259 Hellmann
  6. Charles Rudin
    234 Rudin
  7. Bob Tingkan Li
    101 Li
  8. Ai   Ni
    84 Ni
  9. Joshua K Sabari
    29 Sabari
  10. Kathryn Cecilia Arbour
    34 Arbour
  11. Wei-Chu Victoria Lai
    17 Lai
  12. Michael David Offin
    47 Offin
  13. Ruqin Chen
    2 Chen
  14. Chebli Mrad
    2 Mrad