دورية أكاديمية

Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC

التفاصيل البيبلوغرافية
العنوان: Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC
المؤلفون: Tumeh, Paul C, Hellmann, Matthew D, Hamid, Omid, Tsai, Katy K, Loo, Kimberly L, Gubens, Matthew A, Rosenblum, Michael, Harview, Christina L, Taube, Janis M, Handley, Nathan, Khurana, Neharika, Nosrati, Adi, Krummel, Matthew F, Tucker, Andrew, Sosa, Eduardo V, Sanchez, Phillip J, Banayan, Nooriel, Osorio, Juan C, Nguyen-Kim, Dan L, Chang, Jeremy, Shintaku, I Peter, Boasberg, Peter D, Taylor, Emma J, Munster, Pamela N, Algazi, Alain P, Chmielowski, Bartosz, Dummer, Reinhard, Grogan, Tristan R, Elashoff, David, Hwang, Jimmy, Goldinger, Simone M, Garon, Edward B, Pierce, Robert H, Daud, Adil
المصدر: Cancer Immunology Research, vol 5, iss 5
بيانات النشر: eScholarship, University of California
سنة النشر: 2017
المجموعة: University of California: eScholarship
مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Immunology, Digestive Diseases, Clinical Research, Cancer, Lung, Lung Cancer, Liver Disease, Adult, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological, CD8-Positive T-Lymphocytes, Carcinoma, Non-Small-Cell Lung, Disease-Free Survival, Female, Humans, Kaplan-Meier Estimate, Liver Neoplasms, Lung Neoplasms, Lymphocytes, Tumor-Infiltrating, Male
جغرافية الموضوع: 417 - 424
الوصف: 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. Cancer Immunol Res; 5(5); 417-24. ©2017 AACR.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: unknown
العلاقة: qt6qg0w4sn; https://escholarship.org/uc/item/6qg0w4snTest
الإتاحة: https://escholarship.org/uc/item/6qg0w4snTest
حقوق: public
رقم الانضمام: edsbas.E409D3E1
قاعدة البيانات: BASE