Five-Year Survival and Correlates Among Patients With Advanced Melanoma, Renal Cell Carcinoma, or Non–Small Cell Lung Cancer Treated With Nivolumab

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Abstract

This secondary analysis of the phase 1 CA209-003 clinical trial assesses the 5-year survival and other related factors among patients with advanced melanoma, renal cell carcinoma, or non–small cell lung cancer receiving nivolumab.

Key Points

Question

What is the 5-year survival, and what factors are associated with 5-year survival among patients with advanced melanoma, renal cell carcinoma, or non–small cell lung cancer receiving nivolumab?

Findings

In this secondary analysis of 270 patients from the CA209-003 clinical trial with advanced melanoma, renal cell carcinoma, or non–small cell lung cancer, 5-year survival was negatively associated with presence of bone or liver metastases and positively associated with Eastern Cooperative Oncology Group performance status of 0, objective response, degree of tumor burden reduction, and adverse event occurrence.

Meaning

Nivolumab treatment may be associated with durable survival among some heavily pretreated patients with advanced melanoma, renal cell carcinoma, or non–small cell lung cancer; characterizing factors associated with long-term survival may guide future anti–programmed cell death 1–based clinical trial design.

Abstract

Importance

Nivolumab, a monoclonal antibody that inhibits programmed cell death 1, is approved by the US Food and Drug Administration for treating advanced melanoma, renal cell carcinoma (RCC), non–small cell lung cancer (NSCLC), and other malignancies. Data on long-term survival among patients receiving nivolumab are limited.

Objectives

To analyze long-term overall survival (OS) among patients receiving nivolumab and identify clinical and laboratory measures associated with tumor regression and OS.

Design, Setting, and Participants

This was a secondary analysis of the phase 1 CA209-003 trial (with expansion cohorts), which was conducted at 13 US medical centers and included 270 patients with advanced melanoma, RCC, or NSCLC who received nivolumab and were enrolled between October 30, 2008, and December 28, 2011. The analyses were either specified in the original protocol or included in subsequent protocol amendments that were implemented between 2008 and 2012. Statistical analysis was performed from October 30, 2008, to November 11, 2016.

Intervention

In the CA209-003 trial, patients received nivolumab (0.1-10.0 mg/kg) every 2 weeks in 8-week cycles for up to 96 weeks, unless they developed progressive disease, achieved a complete response, experienced unacceptable toxic effects, or withdrew consent.

Main Outcomes and Measures

Safety and activity of nivolumab; OS was a post hoc end point with a minimum follow-up of 58.3 months.

Results

Of 270 patients included in this analysis, 107 (39.6%) had melanoma (72 [67.3%] male; median age, 61 [range, 29-85] years), 34 (12.6%) had RCC (26 [76.5%] male; median age, 58 [range, 35-74] years), and 129 (47.8%) had NSCLC (79 [61.2%] male; median age, 65 [range, 38-85] years). Overall survival curves showed estimated 5-year rates of 34.2% among patients with melanoma, 27.7% among patients with RCC, and 15.6% among patients with NSCLC. In a multivariable analysis, the presence of liver (odds ratio [OR], 0.31; 95% CI, 0.12-0.83; P = .02) or bone metastases (OR, 0.31; 95% CI, 0.10-0.93; P = .04) was independently associated with reduced likelihood of survival at 5 years, whereas an Eastern Cooperative Oncology Group performance status of 0 (OR, 2.74; 95% CI, 1.43-5.27; P = .003) was independently associated with an increased likelihood of 5-year survival. Overall survival was significantly longer among patients with treatment-related AEs of any grade (median, 19.8 months; 95% CI, 13.8-26.9 months) or grade 3 or more (median, 20.3 months; 95% CI, 12.5-44.9 months) compared with those without treatment-related AEs (median, 5.8 months; 95% CI, 4.6-7.8 months) ( P < .001 for both comparisons based on hazard ratios).

Conclusions and Relevance

Nivolumab treatment was associated with long-term survival in a subset of heavily pretreated patients with advanced melanoma, RCC, or NSCLC. Characterizing factors associated with long-term survival may inform treatment approaches and strategies for future clinical trial development.

Trial Registration

ClinicalTrials.gov identifier: NCT00730639

Related collections

Most cited references 37

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Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

F. Stephen Hodi, Steven J O'Day, David F McDermott … (2010)

An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab--which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response--administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)

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Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.

Suzanne Topalian, F. Stephen Hodi, Julie Brahmer … (2012)

Blockade of programmed death 1 (PD-1), an inhibitory receptor expressed by T cells, can overcome immune resistance. We assessed the antitumor activity and safety of BMS-936558, an antibody that specifically blocks PD-1. We enrolled patients with advanced melanoma, non-small-cell lung cancer, castration-resistant prostate cancer, or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks. Response was assessed after each 8-week treatment cycle. Patients received up to 12 cycles until disease progression or a complete response occurred. A total of 296 patients received treatment through February 24, 2012. Grade 3 or 4 drug-related adverse events occurred in 14% of patients; there were three deaths from pulmonary toxicity. No maximum tolerated dose was defined. Adverse events consistent with immune-related causes were observed. Among 236 patients in whom response could be evaluated, objective responses (complete or partial responses) were observed in those with non-small-cell lung cancer, melanoma, or renal-cell cancer. Cumulative response rates (all doses) were 18% among patients with non-small-cell lung cancer (14 of 76 patients), 28% among patients with melanoma (26 of 94 patients), and 27% among patients with renal-cell cancer (9 of 33 patients). Responses were durable; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up. To assess the role of intratumoral PD-1 ligand (PD-L1) expression in the modulation of the PD-1-PD-L1 pathway, immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients. Of 17 patients with PD-L1-negative tumors, none had an objective response; 9 of 25 patients (36%) with PD-L1-positive tumors had an objective response (P=0.006). 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. Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00730639.).

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The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer.

Peter Goldstraw, Kari Chansky, John Crowley … (2016)

The IASLC Staging and Prognostic Factors Committee has collected a new database of 94,708 cases donated from 35 sources in 16 countries around the globe. This has now been analysed by our statistical partners at Cancer Research And Biostatistics and, in close collaboration with the members of the committee proposals have been developed for the T, N, and M categories of the 8th edition of the TNM Classification for lung cancer due to be published late 2016. In this publication we describe the methods used to evaluate the resultant Stage groupings and the proposals put forward for the 8th edition.

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Author and article information

Journal

Journal ID (nlm-ta): JAMA Oncol

Journal ID (iso-abbrev): JAMA Oncol

Title: JAMA Oncology

Publisher: American Medical Association

ISSN (Print): 2374-2437

ISSN (Electronic): 2374-2445

Publication date (Electronic): 25 July 2019

Publication date (Print): October 2019

Publication date PMC-release: 25 July 2019

Volume: 5

Issue: 10

Pages: 1411-1420

Affiliations

[1 ]Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Bloomberg–Kimmel Institute for Cancer Immunotherapy, Baltimore, Maryland

[2 ]Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts

[3 ]Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Bloomberg–Kimmel Institute for Cancer Immunotherapy, Baltimore, Maryland

[4 ]Department of Internal Medicine (Section of Medical Oncology), Yale Cancer Center, New Haven, Connecticut

[5 ]Department of Internal Medicine, University of Michigan, Ann Arbor

[6 ]Department of Medicine, Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts

[7 ]Carolina BioOncology Institute, Huntersville, North Carolina

[8 ]Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee

[9 ]now with the Department of Medicine (Hematology and Oncology), Northwestern University Medical Center, Chicago, Illinois

[10 ]now with the Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia

[11 ]The Christ Hospital Cancer Center, Cincinnati, Ohio

[12 ]Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, Tennessee

[13 ]Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida

[14 ]Department of Medicine, Memorial Sloan Kettering Cancer Hospital, Weill Cornell Medical College, New York, New York

[15 ]now with the Department of Medicine, Columbia University Irving Medical Center, New York, New York

[16 ]Bristol-Myers Squibb, Princeton, New Jersey

Author notes

Article Information

Accepted for Publication: April 16, 2019.

Published Online: July 25, 2019. doi:10.1001/jamaoncol.2019.2187

Corresponding Author: Suzanne L. Topalian, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Bloomberg–Kimmel Institute for Cancer Immunotherapy, 1550 Orleans St, Cancer Research Bldg 2, Room 508, Baltimore, MD 21287 ( stopali1@ 123456jhmi.edu ).

Author Contributions: Drs Topalian and Sznol had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Topalian, Hodi, Brahmer, Atkins, Carvajal.

Acquisition, analysis, or interpretation of data: Topalian, Hodi, Gettinger, Smith, McDermott, Powderly, Sosman, Atkins, Leming, Spigel, Antonia, Drilon, Wolchok, McHenry, Hosein, Harbison, Grosso, Sznol.

Drafting of the manuscript: Topalian, Gettinger, Hosein, Harbison, Sznol.

Critical revision of the manuscript for important intellectual content: Topalian, Hodi, Brahmer, Gettinger, Smith, McDermott, Powderly, Sosman, Atkins, Leming, Spigel, Antonia, Drilon, Wolchok, Carvajal, McHenry, Harbison, Grosso, Sznol.

Statistical analysis: Gettinger, McHenry, Hosein.

Administrative, technical, or material support: Hodi, Powderly, Sosman, Carvajal, Hosein, Harbison, Grosso.

Supervision: Topalian, Hodi, Brahmer, McDermott, Leming, Drilon, Wolchok, Sznol.

Conflict of Interest Disclosures: Dr Topalian reported receiving grants from Bristol-Myers Squibb, Compugen, and Potenza Therapeutics during the conduct of the study; receiving travel reimbursements from Bristol-Myers Squibb, Dragonfly Therapeutics, Five Prime Therapeutics, and Merck; receiving consulting fees from AbbVie, Amgen, Avidity NanoMedicines, Bayer, Camden Nexus, DNAtrix, Dragonfly Therapeutics, Dynavax Technologies, Ervaxx, Five Prime Therapeutics, FLX Bio, ImaginAb, Immunomic Therapeutics, Janssen Pharmaceuticals, MedImmune/AstraZeneca, Merck, Pfizer, Rock Springs Capital, and WindMIL outside the submitted work; receiving stock or stock options from Aduro, Dragonfly Therapeutics, Ervaxx, Five Prime Therapeutics, FLX Bio, Jounce Therapeutics, Potenza Therapeutics, Tizona LLC, and WindMIL; having intellectual property licensed through her institution to Bristol-Myers Squibb, Aduro, Immunomic Therapeutics, NexImmune, and WindMIL; and having patents pending for cancer therapy via a combination of epigenetic modulation and immune modulation, checkpoint blockade and microsatellite instability, and biomarkers useful for determining response to PD-1 blockade therapy. Dr Hodi reported receiving other support from Bristol-Myers Squibb to his institution during the conduct of the study; receiving grants from Bristol-Myers Squibb and Novartis; receiving personal fees from Aduro, Apricity, Bayer, Bristol-Myers Squibb, Compass Therapeutics, EMD Serono, Genentech/Roche, Merck, Novartis, Partners Therapeutics, Pionyr, Pfizer, Rheos, Sanofi, Surface, Takeda, Torque, and Verastem outside the submitted work; and having a patent to Methods for Treating MIA-related Disorders (#20100111973) pending and royalties paid, a patent to Tumor Antigens and Uses Thereof (#7250291) issued, a patent to Compositions and Methods for Identification, Assessment, Prevention, and Treatment of Melanoma Using PD-L1 Isoforms (#20160340407) pending, patents to Therapeutic Peptides (#20160046716, #20240004112, #20170022275, and #20170008962) pending, a patent to Therapeutic Peptides issued, and a patent to Methods of Using Pembrolizumab and Trebananib pending. Dr Brahmer reported receiving grants and having an uncompensated advisory committee/consulting agreement with Bristol-Myers Squibb during conduct of the study; personal fees from Amgen, AstraZeneca/MedImmune, Celgene, Genentech, Janssen Oncology, Eli Lilly, Merck, and Syndax outside the submitted work; serving on the advisory council from Amgen; consulting agreement from Celgene, Eli Lilly, and Merck; serving on the advisory board from AstraZeneca, Genentech, Janssen Oncology, Merck, and Syndax; and receiving grant support from AstraZeneca/MedImmune and Merck. Dr Gettinger reported receiving other support from Bristol-Myers Squibb outside the submitted work. Dr Smith reported receiving grant support from Bristol-Myers Squibb (Medarex) during the conduct of the study and from Astellas, Bayer, Celgene, Incyte, Eli Lilly, ESSA, F. Hoffmann-LaRoche AG, Genentech, Incyte, MedImmune, Medivation (Pfizer), Merck, Millennium, Novartis, OncoMed, and Seattle Genetics outside the submitted work. Dr McDermott reported receiving grant support and personal fees from Bristol-Myers Squibb during the conduct of the study and receiving honoraria for consulting from Array BioPharm, Bristol-Myers Squibb, Eisai, Exelixis, Genentech BioOncology, Jounce Therapeutics, Merck, Novartis, Pfizer, and Prometheus outside the submitted work. Dr Powderly reported other support from Bristol-Myers Squibb during the conduct of the study; receiving other support from Alkermes, Arcus, AstraZeneca/MedImmune, Corvus, Curis, EMD Serono, FLX Bio, Genentech, InCyte, MacroGenics, Merck, Tempest, and Top Alliance BioSciences outside the submitted work; and having a patent pending and reported being founder and owner of Carolina BioOncology Institute, PLLC, an independent Phase I Cancer Research Clinic and BioCytics Inc, a Human Applications laboratory developing cellular immunotherapies (both companies collaborate with multiple potential biopharma and biotech partners to develop future cellular immunotherapies). Dr Sosman reported receiving personal fees from Bristol-Myers Squibb, Curis, and Genentech outside the submitted work. Dr Atkins reported receiving research support (to the institution) from Bristol-Myers Squibb, Merck, Pfizer and Genentech; serving as a consultant or advisor at Bristol-Myers Squibb, Merck, Novartis, Pfizer, Genentech/Roche, Exelixis, Eisai, Aveo, Array, Arrowhead, AstraZeneca, Ideera, Aduro, ImmunoCore, Boehringer Ingelheim, Iovance, Newlink, Surface, Alexion, Acceleron, Lynx, Cota, Amgen, Galactone, Werewolf, Fathom, Pneuma, and Leads; and having stock options in Werewolf and Pyxis Oncology outside the submitted work. Dr Leming reported receiving consulting fees from Bristol-Myers Squibb for participation in an unrelated consensus panel. Dr Spigel reported receiving grants and other support from Bristol-Myers Squibb during the conduct of the study; having a leadership role at Centennial Medical Center; serving as a consultant or advisor at AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, Evelo, Foundation Medicine, GlaxoSmithKline, Genentech/Roche, Illumina, Eli Lilly, Merck, Moderna Therapeutics, Nektar, Novartis, Pfizer, PharmaMar, Precision Oncology, Takeda, and TRM Oncology; receiving research funding (payments to institution) from AbbVie, Acerta Pharma, Aeglea Biotherapeutics, Amgen, ARMO Biosciences, Astellas, Boehringer Ingelheim, Celgene, Celldex, Clovis Oncology, Daiichi Sankyo, EMD Serono, Foundation Medicine, G1 Therapeutics, Genentech/Roche, Novartis, GlaxoSmithKline, GRAIL, Ipsen, Eli Lilly, Millennium, Nektar, Neon Therapeutics, Oncogenex, Pfizer, Takeda, Tesaro, Transgene, and UT Southwestern; and receiving reimbursement for accommodations, expenses and travel from AstraZeneca, Boehringer Ingelheim, Celgene, EMD Serono, Genentech, Genzyme, Intuitive Surgical, Eli Lilly, Merck, Pfizer, Purdue Pharma, Spectrum Pharmaceuticals, and Sysmex. Dr Antonia reported receiving grants and personal fees from Bristol-Myers Squibb during the conduct of the study; receiving grants from AstraZeneca; receiving personal fees from Amgen, Boehringer Ingelheim, CBMG, Celsius, FLX Bio, Genentech, MedImmune, Memgen, Merck, Multivir, and Venn outside the submitted work; and holding a patent to p53-DC vaccine issues and license and a patent to oncolytic virus pending. Dr Drilon reported receiving personal fees from Ariad, AstraZeneca, Bayer, BeiGene, BergenBio, Blueprint Medicines, Exelixis, Genentech, Helsinn, Hengrui, Ignyta, Loxo, Millenium, MORE Health, Pfizer, Roche, Takeda, TP Therapeutics, Tyra, and Verastem during the conduct of the study; receiving other support from GlaxoSmithKline, Taiho, and Teva outside the submitted work; receiving royalties from Wolters Kluwer for Pocket Medicine; receiving research funding from Foundation Medicine; receiving food and beverage from Merck and Puma; and receiving continuing medical education honoraria from Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, and Research to Practice all outside the submitted work. Dr Wolchok reported receiving grants and personal fees from Bristol-Myers Squibb during the conduct of the study; receiving grants from Bristol-Myers Squibb, MedImmune, and Genentech; receiving personal fees from Adaptive Biotech, Advaxis, Amgen, Apricity, Array BioPharma, Ascentage Pharma, Astellas, Bayer, BeiGene, Bristol-Myers Squibb, Celgene, Chugai, Elucida, Eli Lilly, Esanex, F Star, Genentech, Imvaq, Janssen, Kleo Pharma, Linneaus, MedImmune, Merck, Neon Therapuetics, Ono, Polaris Pharma, Polynoma, Psioxus, Puretech, Recepta, Trieza, Sellas Life Sciences, Serametrix, Surface Oncology, and Syndax outside the submitted work; and owning equity in Potenza Therapeutics, Tizona Pharmaceuticals, Adaptive Biotechnologies, Elucida, Imvaq, BeiGene, Trieza, and Linneaus. Dr Carvajal reported receiving grants and personal fees from Bristol-Myers Squibb during the conduct of the study; receiving grants from Amgen, Astellis, AstraZeneca, Aura Biosciences, Bayer, Bellicum, Corvus, Incyte, Eli Lilly, Macrogenics, Merck, Mirati, Novartis, Roche/Genentech, Pfizer, and Plexxikon outside the submitted work; and receiving personal fees from Aura Biosciences, Chimeron, Incyte, Merck, PureTech, Regenix, Sanofi Genzyme, and Sorrento Therapeutics outside the submitted work. Drs McHenry, Harbison, and Hosein reported stock ownership and employment by Bristol-Myers Squibb. Dr Grosso reported employment by Bristol-Myers Squibb. Dr Sznol reported receiving other support from Bristol-Myers Squibb during the conduct of the study; receiving other support from Amphivena, Adaptive Biotechnologies, Intensity, Actym, Nextcure, and Torque; and receiving consulting fees from Bristol-Myers Squibb, Roche/Genentech, AstraZeneca/Medimmune, Pfizer, Novartis, Kyowa-Kirin, Seattle Genetics, Nektar, Pierre-Fabre, Eli Lilly, Merck US, Teravance, Biodesix, Vaccinex, Janssen, Modulate Therapeutics, Baxalta-Shire, Incyte, Newlink Genetics, Iovance, Agonox, Arbutus, Celldex, Inovio, Gritstone, Molecular Partners, Innate Pharma, AbbVie, Immunocore, Genmab, Almac, Hinge, Allakos, Anaeropharma, Array, GI Innovation, Genocea, Chugai-Roche, Symphogen, Adaptimmune, Omniox, Lycera, and Pieris outside the submitted work. No other disclosures were reported.

Funding/Support: This study was sponsored by Bristol-Myers Squibb.

Role of the Funder/Sponsor: Bristol-Myers Squibb was involved in the design and conduct of the study and the collection, management, analysis, and interpretation of the data. Authors employed by Bristol-Myers Squibb were involved in the preparation, review, and approval of the manuscript.

Additional Contributions: We thank the patients and their families, as well as the investigators and participating study teams. Joel Jiang, PhD, received compensation when formerly employed by Bristol-Myers Squibb for his help with original data analyses and early development of the manuscript. Richard Daniel, PhD, and Lawrence Hargett, BSc, of PPSI (a Parexel company), provided professional medical writing and editorial assistance; the work provided for their company (PPSI) was funded by Bristol-Myers Squibb.

Meeting Presentation: This paper was presented in part at the 32nd Annual Meeting of the Society for Immunotherapy of Cancer, National Harbor, MD; November 11, 2017.

Article

Publisher ID: coi190053

DOI: 10.1001/jamaoncol.2019.2187

PMC ID: 6659167

PubMed ID: 31343665

SO-VID: 01d74df2-734f-430c-a118-c4228a0e754b

License:

This is an open access article distributed under the terms of the CC-BY-NC-ND License.

Five-Year Survival and Correlates Among Patients With Advanced Melanoma, Renal Cell Carcinoma, or Non–Small Cell Lung Cancer Treated With Nivolumab

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Abstract

Key Points

Question

Findings

Meaning

Abstract

Importance

Objectives

Design, Setting, and Participants

Intervention

Main Outcomes and Measures

Results

Conclusions and Relevance

Trial Registration

Related collections

Inflamed lung in vitro co-culture models

Most cited references 37

Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.

The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer.

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