Liver metastasis and treatment outcome with anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC Journal Article
| Authors: | 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.; Chang, J.; Shintaku, I. P.; Boasberg, P. D.; Taylor, E. J.; Munster, P. N.; Algazi, A. P.; Chmielowski, B.; Dummer, R.; Grogan, T. R.; Elashoff, D.; Hwang, J.; Goldinger, S. M.; Garon, E. B.; Pierce, R. H.; Daud, A. |
| Article Title: | Liver metastasis and treatment outcome with anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC |
| 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. © 2017 American Association for Cancer Research. |
| Journal Title: | Cancer Immunology Research |
| Volume: | 5 |
| Issue: | 5 |
| ISSN: | 2326-6066 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2017-05-01 |
| Start Page: | 417 |
| End Page: | 424 |
| Language: | English |
| DOI: | 10.1158/2326-6066.cir-16-0325 |
| PROVIDER: | scopus |
| PUBMED: | 28411193 |
| PMCID: | PMC5749922 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 June 2017 -- Source: Scopus |
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