Liver metastasis and treatment outcome with anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC

Paul C. Tumeh, Matthew D. Hellmann, Omid Hamid, Katy K. Tsai, Kimberly L. Loo, Matthew A. Gubens, Michael Rosenblum, Christina L. Harview, Janis M. Taube, Nathan Handley, Neharika Khurana, Adi Nosrati, Matthew F. Krummel, Andrew Tucker, Eduardo V. Sosa, Phillip J. Sanchez, Nooriel Banayan, Juan C. Osorio, Dan L. Nguyen-Kim, Jeremy ChangI. Peter Shintaku, Peter D. Boasberg, Emma J. Taylor, Pamela N. Munster, Alain P. Algazi, Bartosz Chmielowski, Reinhard Dummer, Tristan R. Grogan, David Elashoff, Jimmy Hwang, Simone M. Goldinger, Edward B. Garon, Robert H. Pierce, Adil Daud

Research output: Contribution to journalArticle

Abstract

We explored the association between liver metastases, tumor CD8+ T-cell count, and response in patients with melanoma or lung cancer treated with the anti-PD-1 antibody, pembrolizumab. The melanoma discovery cohort was drawn from the phase I Keynote 001 trial, whereas the melanoma validation cohort was drawn from Keynote 002, 006, and EAP trials and the non-small cell lung cancer (NSCLC) cohort from Keynote 001. Liver metastasis was associated with reduced response and shortened progression-free survival [PFS; objective response rate (ORR), 30.6%; median PFS, 5.1 months] compared with patients without liver metastasis (ORR, 56.3%; median PFS, 20.1 months) P ≤ 0.0001, and confirmed in the validation cohort (P = 0.0006). The presence of liver metastasis significantly increased the likelihood of progression (OR, 1.852; P < 0.0001). In a subset of biopsied patients (n = 62), liver metastasis was associated with reduced CD8+ T-cell density at the invasive tumor margin (liver metastasis+ group, n = 547 ± 164.8; liver metastasis- group, n = 1,441 ± 250.7; P < 0.016). A reduced response rate and shortened PFS was also observed in NSCLC patients with liver metastasis [median PFS, 1.8 months; 95% confidence interval (CI), 1.4-2.0], compared with those without liver metastasis (n = 119, median PFS, 4.0 months; 95% CI, 2.1-5.1), P = 0.0094. Thus, liver metastatic patients with melanoma or NSCLC that had been treated with pembrolizumab were associated with reduced responses and PFS, and liver metastases were associated with reduced marginal CD8+ T-cell infiltration, providing a potential mechanism for this outcome.

Original languageEnglish (US)
Pages (from-to)417-424
Number of pages8
JournalCancer Immunology Research
Volume5
Issue number5
DOIs
StatePublished - May 2017

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

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    Tumeh, P. C., Hellmann, M. D., Hamid, O., Tsai, K. K., Loo, K. L., Gubens, M. A., Rosenblum, M., Harview, C. L., Taube, J. M., Handley, N., Khurana, N., Nosrati, A., Krummel, M. F., Tucker, A., Sosa, E. V., Sanchez, P. J., Banayan, N., Osorio, J. C., Nguyen-Kim, D. L., ... Daud, A. (2017). Liver metastasis and treatment outcome with anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC. Cancer Immunology Research, 5(5), 417-424. https://doi.org/10.1158/2326-6066.CIR-16-0325