Title |
Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC
|
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Published in |
Cancer Immunology Research, May 2017
|
DOI | 10.1158/2326-6066.cir-16-0325 |
Pubmed ID | |
Authors |
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 Chang, I. 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 |
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 to 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 (odds ratio 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 = 547164.8; liver metastasis -group, n = 1441250.7 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% CI 1.4-2.0), compared to 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 10 | 56% |
United Arab Emirates | 1 | 6% |
France | 1 | 6% |
Italy | 1 | 6% |
Unknown | 5 | 28% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 12 | 67% |
Scientists | 3 | 17% |
Practitioners (doctors, other healthcare professionals) | 2 | 11% |
Science communicators (journalists, bloggers, editors) | 1 | 6% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 194 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 42 | 22% |
Student > Ph. D. Student | 24 | 12% |
Other | 20 | 10% |
Student > Doctoral Student | 15 | 8% |
Student > Bachelor | 11 | 6% |
Other | 24 | 12% |
Unknown | 58 | 30% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 62 | 32% |
Biochemistry, Genetics and Molecular Biology | 24 | 12% |
Immunology and Microbiology | 11 | 6% |
Agricultural and Biological Sciences | 11 | 6% |
Pharmacology, Toxicology and Pharmaceutical Science | 6 | 3% |
Other | 11 | 6% |
Unknown | 69 | 36% |