1229PD - Smoking history and response to nivolumab in patients with advanced NSCLCs

Date 29 September 2014
Event ESMO 2014
Session NSCLC, metastatic
Topics Non-Small-Cell Lung Cancer, Metastatic
Cancer Immunology and Immunotherapy
Presenter Matthew Hellmann
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors M.D. Hellmann1, B.C. Creelan2, K. Woo3, C.S. Sima3, W.T. Iams4, S.J. Antonia5, L. Horn6, J.R. Brahmer7, S. Gettinger8, C. Harbison9, N. Rizvi1
  • 1Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 2Department Of Medical Oncology, H. Lee Moffitt Cancer Center, Tampa/US
  • 3Department Of Epidemiology And Biostatistics, Memorial Sloan Kettering Cancer Center, New York/US
  • 4Medince, Vanderbild-Ingram Cancer Center, Nashville/US
  • 5Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, 33612 - Tampa/US
  • 6Thoracic Oncology Program, Vanderbilt-Ingram Cancer Center, Nashville/US
  • 7Medical Oncology, Sidney Kimmel Cancer Center at Johns Hopkins University, Baltimore/US
  • 8Thoracic Oncology Program, Yale University School of Medicine, 06520-8032 - New Haven/US
  • 9N/a, Bristol-Myers Squibb, Princeton/US

Abstract

Aim

Robust responses to nivolumab (Nivo, anti-PD1 antibody) are seen in both melanomas and NSCLCs. Both of these cancers are characterized by high somatic mutation burden, suggesting a potential link between mutational burden and immunogenicity. Since smoking-related NSCLCs have significantly greater mutation burden compared to never smokers, we hypothesized that smoking history may be associated with response to nivolumab in pts with NSCLCs.

Methods

Smoking status, histology, and EGFR/KRAS genotype were recorded from 88 of 129 pretreated, advanced NSCLCs treated with Nivo monotherapy at 5 of 11 centers that participated in a previously reported study (NCT00730639, Topalian et al, NEJM 2012). Self-reported smoking history was categorized as never (<100 cigarettes), minimal (≤5 pk-yrs), former (>5 pk-yrs, quit > 1 yr prior), or current smokers. In smokers, time-since-quitting was also recorded. Response was assessed every 8 wks by RECIST v1.0. Associations between smoking, histology, genotype, and response were assessed using the Fisher's exact, unpaired T-, log-rank tests.

Results

The response rate was significantly higher in former/current smokers (20/75, 27%, 95% CI 17-38%) vs minimal/never smokers (0/13, 0%, 95% CI 0-25%) (p = 0.034). Responders had significantly more tobacco exposure than non-responders (median 50 pk-yrs [range 15-150] vs 36 pk-yrs [range 0-100], p = 0.036). Among smokers, there was no association between response and time-since-quitting (Current smokers ORR 27%; Quit 1-15 yrs ago 24%; Quit >15 yrs ago 24%, p = 0.18). There was no significant difference in response rate in adeno vs squamous histology (16 vs 21%, p = 0.58). In adenos, response rates in EGFR muts vs KRAS muts vs all others were 1/9 vs 3/13 vs 4/27; the one EGFR mut responder was a 40 pk-yr current smoker.

Conclusions

In advanced NSCLCs, the response rate to Nivo was significantly higher in former/current smokers compared to never/minimal smokers. There were no objective responses in never or minimal smokers in this subset of pts. Smoking history should be considered as a stratification factor for trials of PD-1 pathway inhibitors in lung cancer. Further work is needed to identify the underlying basis of this differential response rate.

Disclosure

S.J. Antonia: Dr. Antonia receives research funding and/or serves as an advisor for Bristol-Myers Squibb. L. Horn: Dr. Horn receives research funding and/or serves as an advisor for Bristol-Myers Squibb; J.R. Brahmer: Dr. Brahmer receives research funding and serves as an advisor for Bristol-Myers Squibb; S. Gettinger: Dr. Gettinger receives research funding and serves as an advisor for Bristol-Myers Squibb; C. Harbison: Dr. Harbison is an employee and stock holder of Bristol-Myers Squibb; N. Rizvi: Dr. Rizvi receives research funding and serves as an advisor for Bristol-Myers Squibb. All other authors have declared no conflicts of interest.