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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References
More filters
Journal ArticleDOI
New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)
Elizabeth Eisenhauer,P. Therasse,Jan Bogaerts,Lawrence H. Schwartz,Daniel J. Sargent,Robert Ford,Janet Dancey,S. Arbuck,S. Gwyther,Margaret M. Mooney,Larry Rubinstein,Lalitha K. Shankar,Lori E. Dodd,Robert M. Kaplan,Denis Lacombe,Jaap Verweij +15 more
TL;DR: The revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions, and a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included.
Journal ArticleDOI
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L. Topalian,F. Stephen Hodi,Julie R. Brahmer,Scott N. Gettinger,David Smith,David F. McDermott,John D. Powderly,Richard D. Carvajal,Jeffrey A. Sosman,Michael B. Atkins,Philip D. Leming,David R. Spigel,Scott J. Antonia,Leora Horn,Charles G. Drake,Drew M. Pardoll,Lieping Chen,William H. Sharfman,Robert A. Anders,Janis M. Taube,Tracee L. McMiller,Haiying Xu,Alan J. Korman,Maria Jure-Kunkel,Shruti Agrawal,Dan McDonald,Georgia Kollia,Ashok Kumar Gupta,Jon M. Wigginton,Mario Sznol +29 more
TL;DR: Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use.
Journal ArticleDOI
The blockade of immune checkpoints in cancer immunotherapy
TL;DR: Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
Journal ArticleDOI
Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer
Hossein Borghaei,Luis Paz-Ares,Leora Horn,D. R. Spigel,M. Steins,Neal Ready,L.Q. Chow,Everett E. Vokes,Enriqueta Felip,Esther Holgado,F. Barlesi,M. Kohlhufl,Oscar Arrieta,Marco Angelo Burgio,J. Fayette,H. Lena,Elena Poddubskaya,David E. Gerber,Scott N. Gettinger,Charles M. Rudin,Naiyer A. Rizvi,L. Crina,G. R. Blumenschein,Scott J. Antonia,C. Dorange,C. T. Harbison,F. Graf Finckenstein,Julie R. Brahmer +27 more
TL;DR: Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression (≥1, ≥5%, and ≥10%) of the PD-1 ligand.
Journal ArticleDOI
Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer
Julie R. Brahmer,Scott S. Tykodi,Scott S. Tykodi,Laura Q.M. Chow,Wen-Jen Hwu,Suzanne L. Topalian,Patrick Hwu,Charles G. Drake,Luis H. Camacho,John S. Kauh,Kunle Odunsi,Henry C. Pitot,Omid Hamid,Shailender Bhatia,Renato G. Martins,Keith D. Eaton,Shuming Chen,Theresa M. Salay,Suresh Alaparthy,Joseph F. Grosso,Alan J. Korman,Susan M. Parker,Shruti Agrawal,Stacie M. Goldberg,Drew M. Pardoll,Ashok Kumar Gupta,Jon M. Wigginton +26 more
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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