663P - First-line nivolumab + cabozantinib vs sunitinib in patients (pts) with advanced renal cell carcinoma (aRCC) in subgroups based on prior nephrectomy in the CheckMate 9ER trial

Background

First-line (1L) nivolumab + cabozantinib (N+C) significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) vs sunitinib (S) in aRCC pts in the phase III CheckMate 9ER trial. Pts without upfront nephrectomy have poor prognoses and clinical trial data in this population remain limited. Assessment of how different baseline characteristics may impact outcomes with N+C vs S in aRCC pts is of clinical interest.

Methods

Pts with any IMDC risk and clear cell aRCC were randomized to N 240 mg IV Q2W + C 40 mg PO QD vs S 50 mg PO QD (4 weeks of 6-week cycles). In this post hoc exploratory analysis, efficacy was evaluated in subgroups with and without prior nephrectomy. PFS and ORR were assessed per RECIST v1.1 by blinded independent central review.

Results

Of 651 intent-to-treat (ITT) pts, 455 had prior nephrectomy (N+C, n = 222; S, n = 233) and 196 had no prior nephrectomy (N+C, n = 101; SUN, n = 95). Of pts with prior nephrectomy, 24.3% (N+C) and 30.9% (S) underwent nephrectomy within 3 months of enrollment. Baseline characteristics were generally balanced between arms within subgroups. Versus pts without prior nephrectomy, a higher proportion of pts with prior nephrectomy had a lower tumor burden, more favorable IMDC risk scores, and derived greater efficacy benefits with either N+C or S. Notably, N+C improved PFS, ORR, complete response, and response durability outcomes vs S regardless of nephrectomy status (Table). Of evaluable pts without prior nephrectomy, median reduction in target kidney lesions was 30% (N+C; n = 53) vs 16% (S; n = 51). OS benefits were observed with N+C vs S in pts with prior nephrectomy; longer follow-up is needed to characterize OS outcomes between arms in pts without prior nephrectomy. Table: 663P

^aData based on minimum follow-up of 16 mo (median 23.5 mo) for OS in ITT pts, acknowledging censoring at later timepoints. CR, complete response; NE, not estimable; NR, not reached.

Conclusions

N+C provided improved efficacy benefits vs S in pts with and without prior nephrectomy. These results continue to support N+C as a 1L treatment option for pts with aRCC.

Clinical trial identification

NCT03141177.

Editorial acknowledgement

Professional medical writing assistance was provided by Jen Tyson, PhD, of Parexel, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol-Myers Squibb Company (Princeton, NJ) and Ono Pharmaceutical Company Ltd. (Osaka, Japan); Exelixis Inc. (Alameda, CA), Ipsen Pharma (Paris, France), and Takeda Pharmaceutical Company Ltd. (Osaka, Japan).

Disclosure

C.G. Porta: Financial Interests, Personal, Invited Speaker, Seminars to Medical Direction Personnel on kidney cancer: Angelini; Financial Interests, Personal, Advisory Board, Consultancy relative to urogenital cancers: AstraZeneca; Financial Interests, Personal, Advisory Board, Advisor relative to development of therapeutics in GU Oncology; speaker at BMS-sponsored meetings; protocol steering committee member: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Advisor role relative to the development of Lenvatinib in RCC and HCC; protocol steering committee member: Eisai; Financial Interests, Personal, Invited Speaker, Expert testimony at AIFA; speaker in EUSA-sponsored meetings; advisor relative to the development of Tivozanib; protocol steering committee member: EUSA; Financial Interests, Personal, Invited Speaker, Speaker at GE-sponsored meeting relative to the renal toxicity of CT contrast medium; writing engagement: General Electric; Financial Interests, Personal, Invited Speaker, Speaker at Ipsen-sponsored meeting; advisor relative to the development of Cabozantinib in RCC: Ipsen; Financial Interests, Personal, Invited Speaker, Speaker at Janssen-sponsored meetings: Janssen; Financial Interests, Personal, Advisory Board, Advisor relative to the development of Avelumab in GU malignancies: Merck; Financial Interests, Personal, Advisory Board, Advisor relative to the development of Pembrolizumab and Belzutifan in RCC; Speaker at MSD-sponsored meetings: MSD; Financial Interests, Personal, Invited Speaker, Speaker at Novartis-sponsored meetings: Novartis; Financial Interests, Personal, Expert Testimony, Expert testimony at EMA; consultant for GU Oncology portfolio; Speaker at Pfizer-sponsored meetings: Pfizer; Financial Interests, Personal, Invited Speaker, Member of the Steering Committee of ipi/Nivo EAP in Italy: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, Steering Committee Member of CLEAR study: Eisai; Financial Interests, Personal, Invited Speaker, Steering Committee member for Tivozanib Italian EAP: EUSA; Other, Other, Travel support: Roche. M. Burotto: Financial Interests, Personal, Invited Speaker: Aztrazeneca; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche. C. Suarez Rodriguez: Financial Interests, Personal, Invited Speaker: Astellas Pharma; Financial Interests, Personal, Advisory Board: Astellas Pharma; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Eusa Pharma; Financial Interests, Personal, Invited Speaker: Hoffmann-La Roche LTD; Financial Interests, Personal, Advisory Board: Hoffmann-La Roche LTD; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer S.L.U.; Financial Interests, Personal, Advisory Board: Pfizer S.L.U.; Financial Interests, Personal, Advisory Board: Sanofi-Aventis; Financial Interests, Institutional, Research Grant: AB Science; Financial Interests, Institutional, Research Grant: Aragon Pharmaceuticals; Financial Interests, Institutional, Research Grant: Astellas Pharma; Financial Interests, Institutional, Research Grant: AstraZeneca AB; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Blueprint Medicines corporation; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim Espana, S.A.; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Clovis Oncology; Financial Interests, Institutional, Research Grant: Exelixis INC, F.; Financial Interests, Institutional, Research Grant: Genentech INC; Financial Interests, Institutional, Research Grant: Glaxosmithkline, SA; Financial Interests, Institutional, Research Grant: Hoffmann-La Roche LTD; Financial Interests, Institutional, Research Grant: Novartis Farmaceutica S.A.; Financial Interests, Institutional, Research Grant: Pfizer S. L.U.; Financial Interests, Institutional, Research Grant: Sanofi-Aventis. M.T. Bourlon: Financial Interests, Personal, Advisory Board, Role and Honoraria: BMS; Financial Interests, Personal, Advisory Board, Role and Honoraria: Astellas; Financial Interests, Personal, Advisory Board, Role and Honoraria: Ipsen; Financial Interests, Personal, Advisory Board, Role and Honoraria: Novartis; Financial Interests, Personal, Advisory Board, Role and Honoraria: Pfizer; Financial Interests, Personal, Advisory Board, Role and Honoraria: Bayer; Financial Interests, Personal, Advisory Board, Role and Honoraria: Janssen; Financial Interests, Personal, Advisory Board, Role and Honoraria: Merck; Financial Interests, Personal, Advisory Board, Role and Honoraria: MSD; Financial Interests, Personal, Advisory Board, Role and Honoraria: Eisai; Financial Interests, Personal, Invited Speaker, Payment as speaker: BMS; Financial Interests, Personal, Invited Speaker, Payment as speaker: Astellas; Financial Interests, Personal, Advisory Board, Role and Honoraria: Asofamar; Financial Interests, Personal, Invited Speaker, Payment as speaker: Asofamar; Financial Interests, Personal, Invited Speaker, Payment as speaker: Ipsen; Financial Interests, Personal, Invited Speaker, Payment as speaker: Novartis; Financial Interests, Personal, Invited Speaker, Payment as speaker: Pfizer; Financial Interests, Personal, Invited Speaker, Payment as speaker: Bayer; Financial Interests, Personal, Invited Speaker, Payment as speaker: Janssen; Financial Interests, Personal, Invited Speaker, Payment as speaker: Merck; Financial Interests, Personal, Invited Speaker, Payment as speaker: MSD; Financial Interests, Personal, Invited Speaker, Payment as speaker: Eisai; Financial Interests, Personal, Member, PI and steering committee role for BMS trials: BMS; Non-Financial Interests, Personal, Advisory Role, Participated in several activities: BMS; Non-Financial Interests, Personal, Advisory Role, Participated in several activities: Astellas; Non-Financial Interests, Personal, Advisory Role, Participated in several activities: Asofamar; Non-Financial Interests, Personal, Advisory Role, Participated in several activities: Ipsen; Non-Financial Interests, Personal, Advisory Role, Participated in several activities: Novartis; Non-Financial Interests, Personal, Advisory Role, Participated in several activities: Pfizer; Non-Financial Interests, Personal, Advisory Role, Participated in several activities: Bayer; Non-Financial Interests, Personal, Advisory Role, Participated in several activities: Janssen; Non-Financial Interests, Personal, Advisory Role, Participated in several activities: Merck; Non-Financial Interests, Personal, Advisory Role, Participated in several activities: MSD; Non-Financial Interests, Personal, Advisory Role, Participated in several activities: Eisai. J. Hsieh: Financial Interests, Personal, Other, Consultant: BostonGene; Financial Interests, Personal, Other, Consultant: Eisai; Financial Interests, Personal, Stocks/Shares, Consultant: BostonGene; Non-Financial Interests, Institutional, Principal Investigator, Local PI, Trial PI: BMS; Non-Financial Interests, Institutional, Principal Investigator, Local PI, Trial PI: Eisai; Non-Financial Interests, Institutional, Principal Investigator, Coordinating PI, Trial PI: Merck; Non-Financial Interests, Institutional, Principal Investigator, Local PI: SillaJen. A.Y. Shah: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Royalties: EMD Serono. A. Hamzaj: Non-Financial Interests, Personal, Principal Investigator, I have participated in several clinical trials in Kidney Cancer and Urothelial Cancer as a Principal Investigator: BMS; Non-Financial Interests, Personal, Principal Investigator, I have participated in several clinical trials in Prostate Cancer and Urothelial Cancer as a Principal Investigator: Janssen; Non-Financial Interests, Personal, Principal Investigator, I have participated in several clinical trials in Kidney Cancer Prostate Cancer, and Urothelial Cancer as a Principal Investigator: Merck. J. Bedke: Financial Interests, Institutional, Research Grant, Funding to institution for trial conduct: BMS; Financial Interests, Institutional, Research Grant, Funding to institution for trial conduct: Eisai; Financial Interests, Institutional, Research Grant, Funding to institution for trial conduct: Ipsen; Financial Interests, Institutional, Research Grant, Funding to institution for trial conduct: MSD; Financial Interests, Institutional, Research Grant, Funding to institution for trial conduct: Novartis; Financial Interests, Institutional, Research Grant, Funding to institution for trial conduct: Roche; Financial Interests, Institutional, Research Grant, Funding to institution for trial conduct: Exelixis; Financial Interests, Institutional, Research Grant, Funding to institution for trial conduct: Nektar; Financial Interests, Institutional, Research Grant, Funding to institution for trial conduct: Pfizer; Financial Interests, Personal, Other, Funding to institution for trial conduct: BMS; Financial Interests, Personal, Other: Eisai; Financial Interests, Personal, Other: EUSA; Financial Interests, Personal, Other: Ipsen; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Merck; Financial Interests, Personal, Other: Janssen. D. Pook: Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Institutional, Principal Investigator, Local PI: Astellas; Financial Interests, Institutional, Principal Investigator, Local PI: BMS; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Ipsen; Financial Interests, Institutional, Principal Investigator, Local PI: MSD; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Pfizer; Financial Interests, Institutional, Principal Investigator, Local PI: Roche. E.R. Kessler: Financial Interests, Institutional, Principal Investigator, Local PI: BMS; Financial Interests, Institutional, Principal Investigator, Local P: Merck; Financial Interests, Institutional, Principal Investigator, Local P: Pfizer. Y. Tomita: Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Personal, Other, honoraria for lecture at conference: BMS; Financial Interests, Personal, Other, honoraria for lecture at conference: Pfizer; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Personal, Other, honoraria for lecture at conference: Ono Pharmaceutical; Financial Interests, Personal, Other, honoraria for lecture at conference: Astellas. A. Drakaki: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Pack Pharma; Financial Interests, Personal, Advisory Board: Roche Genentech; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Institutional, Principal Investigator, Local PI: AstraZeneca; Financial Interests, Institutional, Principal Investigator, Local PI: BMS; Financial Interests, Institutional, Principal Investigator, Local PI: Infinity; Financial Interests, Institutional, Principal Investigator, Local PI: Kite Pharma; Financial Interests, Institutional, Principal Investigator, Local PI: Merck; Financial Interests, Institutional, Principal Investigator, Local PI: Roche; Financial Interests, Institutional, Principal Investigator, Local PI: Seattle Genetics. J. Zhang: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. B. Simsek: Financial Interests, Personal, Stocks/Shares: BMS; Financial Interests, Personal, Full or part-time Employment: BMS. G. Schwab: Financial Interests, Personal, Member of the Board of Directors, Independent BoD member of Cellerant: Cellerant Therapeutics; Financial Interests, Personal, Officer, President of Product Development and Medical Affairs, Chief Medical Officer: Exelixis Inc; Financial Interests, Personal, Member of the Board of Directors, Independent BoD member of Genocea: Genocea; Financial Interests, Personal, Stocks/Shares, Stock ownership as employee: Exelixis Inc; Financial Interests, Personal, Full or part-time Employment: Exelixis Inc; Financial Interests, Personal, Stocks/Shares, Stock ownership as BoD Compensation package: Genocea. B. Escudier: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Aveo; Financial Interests, Personal, Advisory Board: Eisai. R.J. Motzer: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Aveo Pharmaceuticals; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Genentech/Roche; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Lilly Oncology; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Principal Investigator, Coordinating PI, funding for trial conduct from sponsor to my employer MSKCC: BMS; Financial Interests, Institutional, Principal Investigator, Coordinating PI, funding for trial conduct from sponsor to my employer MSKCC: Eisai; Financial Interests, Institutional, Invited Speaker, Coordinating PI, funding for trial conduct from sponsor to my employer MSKCC: Exelixis; Financial Interests, Institutional, Principal Investigator, Coordinating PI, funding for trial conduct from sponsor to my employer MSKCC: Genentech/Roche; Financial Interests, Institutional, Principal Investigator, Coordinating PI, funding for trial conduct from sponsor to my employer MSKCC: Merck; Financial Interests, Institutional, Principal Investigator, Coordinating PI, funding for trial conduct from sponsor to my employer MSKCC: Pfizer. T.K. Choueiri: Financial Interests, Personal, Invited Speaker, Best of ASCO19 talk: Advent Health; Financial Interests, Personal, Other, Consultant on onc drugs: Analysis Group; Financial Interests, Personal, Advisory Board, Advising oncology strategy: Aptitude Health; Financial Interests, Personal, Invited Speaker, ASCO-related event: ASCO-SITC; Financial Interests, Personal, Invited Speaker, CME, ImmunoOncology in RCC: ASiM, CE; Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: AstraZeneca; Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: BMS; Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: Calithera; Financial Interests, Personal, Invited Speaker, RCC webinar: Cancernet; Financial Interests, Personal, Invited Speaker, CME Podcast in RCC ($500): Caribou Publishing; Financial Interests, Personal, Advisory Board, Advice on Onc drugs: EMD Serono; Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: Exelixis; Financial Interests, Personal, Invited Speaker, CME, Kidney Cancer Association ($1300): France Foundation; Financial Interests, Personal, Advisory Board, Advice on Onc Drugs: Infinity; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker, Reimbursement ($432): Kidney Cancer Association; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker, Grand Rounds: MDACC; Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: Merck; Financial Interests, Personal, Invited Speaker, CME mjhlifesciences.com (OncLive): MJH life sciences; Financial Interests, Personal, Invited Speaker, National Association of Managed Care: NAMC; Financial Interests, Personal, Other, Grant to review Orien Network ($400): ORIEN; Financial Interests, Personal, Invited Speaker, CME, ww2.peerview.com: Peerview; Financial Interests, Personal, Invited Speaker, CME, gotoper.com: PER; Financial Interests, Personal, Advisory Board, Advice on GU?RCC drugs: Pfizer; Financial Interests, Personal, Invited Speaker, CME, RCC: Springer; Financial Interests, Personal, Advisory Board, Advice on GU Onc drugs: Surface Oncology; Financial Interests, Personal, Invited Speaker, Best of ESMO20 talk ($1000): UAE Society of Onc; Financial Interests, Personal, Invited Speaker, CME, RCC: WebMed; Financial Interests, Personal, Stocks/Shares, 10,000 options $0.37/share (2020): Pionyr; Financial Interests, Personal, Stocks/Shares, 100,000 options $0.16/share (2020): Tempest; Financial Interests, Personal, Royalties, For writing and updating chapters in GU Oncology: Up-To-Date online textbook; Financial Interests, Institutional, Funding, National co-chair on 3 ongoing trials: Alliance Cooperative Group; Financial Interests, Institutional, Funding, National chair: AstraZeneca; Financial Interests, Institutional, Funding, National chair: BMS; Financial Interests, Institutional, Research Grant, GU oncology translational research through IIOn program: BMS; Financial Interests, Institutional, Funding, SC member: Eisai; Financial Interests, Institutional, Funding, National co-chair: EMD Serono; Financial Interests, Institutional, Funding, National chair: Exelixis; Financial Interests, Institutional, Research Grant, for GU oncology translational research: Eselixis; Financial Interests, Institutional, Principal Investigator, Local PI: GSK; Financial Interests, Institutional, Funding, Chair of trial: Lilly; Financial Interests, Institutional, Funding, National chair: Merck; Financial Interests, Institutional, Funding, National chair: Peloton; Financial Interests, Institutional, Funding, National co-chair: Pfizer; Financial Interests, Institutional, Principal Investigator, Local PI: Roche; Financial Interests, Institutional, Research Grant, For health outcomes research: Roche; Financial Interests, Institutional, Principal Investigator, Local PI: Surface Oncology; Financial Interests, Institutional, Funding, National chair: Takeda; Financial Interests, Institutional, Funding, National chair: Tracon; Non-Financial Interests, Personal, Leadership Role, Meeting co-chair 2019,2020: Kidney Cancer Research Summit of KidneyCAN; Non-Financial Interests, Personal, Principal Investigator, Trial Global and National PI with GU Cancers, mostly Kidney Cancer: Multiple Academic and Industry entities; Non-Financial Interests, Personal, Other, Grant reviewers: AACR; Non-Financial Interests, Personal, Other, Track Leader/session chair/Speaker/Discussant: ASCO; Non-Financial Interests, Institutional, Other, Access to genomic database: Foundation Med; Non-Financial Interests, Institutional, Other, Access to genomic database: Guardant; Non-Financial Interests, Institutional, Other, Access to genomic database: Invitae; Non-Financial Interests, Personal, Other, Medical writing and editorial assistance support (e.g., Clinical Thinking, Envision Pharma Group, Fishawack Group of Companies, Health Interactions, Parexel, Oxford PharmaGenesis, pharmagenesis and others). However , first draft frequently initiated by myself when I am 1st author: Medical Communication; Non-Financial Interests, Personal, Other, Reviewer of papers (e.g., NEJM, Lancet, JCO): Various journals; Non-Financial Interests, Personal, Other, Speaker/disscussant: ESMO. T.B. Powles: Financial Interests, Personal, Other, Travel accomodation/expenses: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Other, Travel accommodations/expenses: Ipsen; Financial Interests, Personal, Advisory Board: Johnson & Johnson; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Other, Travel accomodations/expenses: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Other, Travel accommodations expenses: Pfizer; Financial Interests, Personal, Other, Travel accommodations/expenses: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: Johnson & Johnson; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Merck Serono; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Seattle Genetics. All other authors have declared no conflicts of interest.