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
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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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Frequency, Morbidity, and Mortality of Bone Metastases in Advanced Hepatocellular Carcinoma
James J. Harding,Ghaith Abu-Zeinah,Joanne F. Chou,Dwight H. Owen,Michele Ly,Maeve A. Lowery,Maeve A. Lowery,Marinela Capanu,Richard Do,Richard Do,Nancy E. Kemeny,Nancy E. Kemeny,Eileen M. O'Reilly,Eileen M. O'Reilly,Leonard B. Saltz,Leonard B. Saltz,Ghassan K. Abou-Alfa,Ghassan K. Abou-Alfa +17 more
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Clinical Characteristics of Liver Metastasis in Nivolumab-treated Patients with Non-small Cell Lung Cancer.
Takayuki Shiroyama,Hidekazu Suzuki,Motohiro Tamiya,Akihiro Tamiya,Ayako Tanaka,Norio Okamoto,Kenji Nakahama,Yoshihiko Taniguchi,Shun-ichi Isa,Takako Inoue,Fumio Imamura,Shinji Atagi,Tomonori Hirashima +12 more
TL;DR: Baseline clinical characteristics were a strong predictor of outcome in nivolumab-treated patients with liver metastasis and were significantly associated with younger age, poorer Eastern Cooperative Oncology Group performance status (ECOG PS), and more metastatic sites.
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AAV-mediated gene transfer of DNase I in the liver of mice with colorectal cancer reduces liver metastasis and restores local innate and adaptive immune response
Yujia Xia,Yujia Xia,Jiayi He,Jiayi He,Hongji Zhang,Han Wang,Han Wang,George Tetz,Casey A. Maguire,Yu Wang,Amblessed E. Onuma,Dmitry Genkin,Victor Tetz,Alexey Stepanov,S. S. Terekhov,V. M. Ukrainskaya,Hai Huang,Allan Tsung +17 more
TL;DR: The data suggest that AAV‐mediated DNase I liver gene transfer is a safe and effective modality to inhibit metastasis and represents a novel therapeutic strategy for CRC.
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Advances in the Treatment of Non-Small Cell Lung Cancer: Immunotherapy.
S. Patel,Jared Weiss +1 more
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Response to Anti-PD-1 in Uveal Melanoma Without High-Volume Liver Metastasis.
Douglas B. Johnson,Riyue Bao,Kristin K. Ancell,Anthony B. Daniels,Deborah Wallace,Jeffrey A. Sosman,Jason J. Luke +6 more
TL;DR: Anti-PD-1-based therapy may cause clinical benefit in metastatic UM, seemingly more often in patients without bulky liver metastases, and lack of mutation burden and T-cell infiltration and MYC overexpression may be factors limiting therapeutic responses.
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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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