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 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 Taylor,Pamela N. Munster,Alain Algazi,Bartosz Chmielowski,Reinhard Dummer,Tristan Grogan,David Elashoff,Jimmy Hwang,Simone M. Goldinger,Edward B. Garon,Robert H. Pierce,Adil Daud +33 more
TLDR
Liver metastatic patients with melanoma or NSCLC that had been treated with pembrolizumab were associated with reduced responses and PFS, and liver metastases wereassociated with reduced marginal CD8+ T-cell infiltration, providing a potential mechanism for this outcome.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. Cancer Immunol Res; 5(5); 417-24. ©2017 AACR.read more
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Journal ArticleDOI
Primary Resistance to PD-1-Based Immunotherapy-A Study in 319 Patients with Stage IV Melanoma.
Teresa Amaral,Olivia Seeber,Edgar Mersi,Stephanie Sanchez,Ioannis Thomas,Andreas Meiwes,Andrea Forschner,Ulrike Leiter,Thomas Eigentler,Ulrike Keim,Claus Garbe +10 more
TL;DR: Melanoma patients with primary resistance to immunotherapy have a dismal prognosis, and response at the first tumor assessment after starting immunotherapy is a stronger prognostic factor for the further course of the disease than pretreatment risk factors.
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HLA-A*26 Is Correlated With Response to Nivolumab in Japanese Melanoma Patients
Yoshihiro Ishida,Atsushi Otsuka,Hidenori Tanaka,Mitchell P. Levesque,Reinhard Dummer,Kenji Kabashima,Kenji Kabashima +6 more
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Heterogeneous Tumor-Immune Microenvironments between Primary and Metastatic Tumors in a Patient with ALK Rearrangement-Positive Large Cell Neuroendocrine Carcinoma.
Takahiro Tashiro,Kosuke Imamura,Yusuke Tomita,Daisuke Tamanoi,Akira Takaki,Kazuaki Sugahara,Ryo Sato,Koichi Saruwatari,Shinya Sakata,Megumi Inaba,Sunao Ushijima,Naomi Hirata,Takuro Sakagami +12 more
TL;DR: In this paper, a 32-year-old female patient with ALK-rearrangement-positive large cell neuroendocrine carcinoma (LCNEC) or anaplastic lymphoma kinase (ALK) rearrangement positive lung cancer was presented.
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High serum LDH and liver metastases are the dominant predictors of primary cancer resistance to anti-PD(L)1 immunotherapy.
Laurent Dercle,Samy Ammari,Elvire Roblin,Amélie Bigorgne,Stéphane Champiat,Lokmane Taihi,Athèna Plaian,Sophie Hans,Sara Lakiss,Lambros Tselikas,Mathieu Rouanne,Eric Deutsch,Lawrence H. Schwartz,Mithat Gönen,Jessica Flynn,Christophe Massard,Jean-Charles Soria,C. Robert,Aurélien Marabelle +18 more
TL;DR: In this article , the authors applied machine learning algorithms and multivariate analyses on baseline medical data to estimate their relative impact on overall survival (OS) upon anti-PD-(L)1 monotherapies.
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Real-World Efficacy and Safety of Anlotinib With and Without Immunotherapy in Advanced Non-Small Cell Lung Cancer.
TL;DR: In this paper, the authors investigated the efficacy and safety of anlotinib with and without immunotherapy in non-small cell lung cancer (NSCLC), and the primary endpoint was progression-free survival (PFS).
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TL;DR: Antibody-mediated blockade of PD-L1 induced durable tumor regression and prolonged stabilization of disease in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer.
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