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
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
Real-World Clinical Outcomes and Prognostic Factors for Patients with Advanced Angiosarcoma who Received Systemic Treatment
Changhee Park,Miso Kim,Yoonjin Kwak,Kyung Chul Moon,Se Hyun Kim,Bhumsuk Keam,Yu Jung Kim,Tae Min Kim,Dong Wan Kim +8 more
TL;DR: In this paper, the authors reviewed electronic medical records of 75 patients with angiosarcoma who were treated with systemic chemotherapy for inoperable or metastatic disease and showed an objective response rate (ORR) of 23.7% (n=14), a median progression-free survival (mPFS) of 4.0 months (95% confidence interval [CI], 3.0 to 6.1), and a median overall survival (MOS) of 10.2 months (mOS) with a tendency for prolonged mOS (13.8 months
Journal ArticleDOI
The Efficacy of PD-1/PD-L1 Inhibitors in Patients with Liver Metastasis of Non-Small Cell Lung Cancer: A Real-World Study
Mingying Xie,Na Li,Xiaoling Xu,Yanjun Xu,Hui Li,Liang-Fei Zhu,Jiamin Sheng,Zichao Zhou,Yun Fan +8 more
TL;DR: PD-1/PD-L1 inhibitors are effective in liver metastasis–NSCLC patients, however, the efficacy is inferior when compared to those of patients without liver metastases.
Journal ArticleDOI
Clinical application status and prospect of the combined anti-tumor strategy of ablation and immunotherapy
Li Yin,Xing-yu Li,Lin-lin Zhu,Gui-lai Chen,Zhuo Xiang,Qing-qing Wang,Jing-wang Bi,Qiang Wang +7 more
TL;DR: It is hoped to provide a new idea and reference for the clinical application of combinate treatment of tumor ablation and immunotherapy and proposed possible solutions for the challenges encountered by combined therapy.
Journal ArticleDOI
Nasopharyngeal Carcinoma Progression: Accumulating Genomic Instability and Persistent Epstein–Barr Virus Infection
Xue Liu,Yayan Deng,Yujuan Huang,Jiaxiang Ye,Si-Yi Xie,Qian He,Yong-Yu Chen,Yan Lin,Rong Liang,Jiazhang Wei,Yongqiang Li,Jinyan Zhang +11 more
TL;DR: A review of the key characteristics of genomic instability in NPC and the profound implications of EBV infection is presented and the significance of profiling genomic instability for the assessment of disease progression and treatment efficacy is discussed.
Journal ArticleDOI
Atezolizumab in understudied populations with bladder cancer
TL;DR: The SAUL trial demonstrates that atezolizumab is safe and efficacious in a patient population that more accurately reflects the real-world scenario, but its benefit might still be limited in historically poorly performing populations.
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.
Related Papers (5)
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
Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer
Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer
Julie R. Brahmer,Karen L. Reckamp,Paul Baas,Lucio Crinò,Wilfried Eberhardt,Elena Poddubskaya,Scott J. Antonia,Adam Pluzanski,Everett E. Vokes,Esther Holgado,David M. Waterhouse,Neal Ready,Justin F. Gainor,Osvaldo Arén Frontera,Libor Havel,Martin Steins,Marina Chiara Garassino,Joachim G.J.V. Aerts,Manuel Domine,Luis Paz-Ares,Martin Reck,Christine Baudelet,Christopher T. Harbison,Brian Lestini,David R. Spigel +24 more
Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Naiyer A. Rizvi,Naiyer A. Rizvi,Matthew D. Hellmann,Matthew D. Hellmann,Alexandra Snyder,Alexandra Snyder,Pia Kvistborg,Vladimir Makarov,Jonathan J. Havel,William Lee,Jianda Yuan,Phillip Wong,Teresa S. Ho,Martin L. Miller,Natasha Rekhtman,Andre L. Moreira,Fawzia Ibrahim,Cameron Bruggeman,Billel Gasmi,Roberta Zappasodi,Yuka Maeda,Chris Sander,Edward B. Garon,Taha Merghoub,Jedd D. Wolchok,Jedd D. Wolchok,Ton N. Schumacher,Timothy A. Chan,Timothy A. Chan +28 more