Abstract 660P
Background
In the phase III CLEAR trial, lenvatinib (L) + pembrolizumab (P) demonstrated significant improvement in PFS (HR 0.39; 95% CI 0.32, 0.49; P<0.001), OS (HR 0.66; 95% CI 0.49, 0.88; P=0.005), and ORR (odds ratio 4.35; 95% CI 3.16, 5.97) vs sunitinib (S) for patients (pts) with aRCC. Here we report efficacy results for L + P vs S in distinct subgroups of pts and provide updated toxicity data.
Methods
Pts were randomized (1:1:1) to receive 1 of 3 treatments including L 20 mg PO QD + P 200 mg IV Q3W and S 50 mg PO QD (4 weeks on/2 weeks off). Pts with or without adverse prognostic features (ie, sarcomatoid histology, bone and/or liver metastasis, and no prior nephrectomy) were considered. Median PFS and OS were calculated using the Kaplan-Meier method; HR and 95% CI comparing PFS (assessed by the independent review committee [IRC]) and OS were estimated by a stratified Cox model. Odds ratios were used to compare ORRs by IRC. Immune-related adverse events (irAEs) and data regarding corticosteroid use were provided.
Results
PFS was consistently and clearly improved with L + P vs S for pts in all subgroups. Additionally, the HR for OS favored L+P vs S across subgroups (Table). ORR was greater with L + P vs S for subgroups with sarcomatoid histology (61% vs 24%; odds ratio: 8.9 [95% CI 2.1, 37.8]), bone metastasis (60% vs 27%; odds ratio: 4.1 [95% CI 2.1, 7.9]), liver metastasis (56% vs 26%; odds ratio: 3.5 [95% CI 1.7, 7.3]) and no prior nephrectomy (63% vs 23%; odds ratio: 6.3 [95% CI 3.1, 12.6]); similar results were seen in pts without these features (to be presented). 52 (14.8%) pts in the L + P group received high-dose corticosteroids (≥40 mg prednisone daily or equivalent) for any duration to manage irAEs.
Conclusions
In pts with aRCC, L + P demonstrated efficacy benefits over S in pts with/without adverse prognostic features, including sarcomatoid histology, bone and/or liver metastasis, and no prior nephrectomy. Only 15% of pts needed high-dose corticosteroids for irAEs. Table: 660P
| Sarcomatoid | Bone mets | Liver mets | Prior nephrectomy | |||||
| Yes L + P (n=28)S (n=21) | No L + P (n=327)S (n=336) | Yes L + P (n=80)S (n=89) | No L + P (n=275)S (n=267) | Yes L + P (n=63)S (n=70) | No L + P (n=292)S (n=286) | Yes L + P (n=262)S (n=275) | No L + P (n=93)S (n=82) | |
| mPFS — mos L + P S HR (95% CI) L+P vs S | 11.1 5.5 0.39 (0.18, 0.84) | 24.3 9.4 0.38 (0.31, 0.48) | 18.4 5.6 0.46 (0.29, 0.71) | 27.6 9.9 0.38 (0.29, 0.48) | 14.6 4.2 0.49 (0.31, 0.77) | 27.6 10.9 0.36 (0.28, 0.47) | 27.7 9.4 0.37 (0.28, 0.47) | 15.3 7.5 0.44 (0.28, 0.68) |
| mOS — mos L + P S HR (95% CI) L+P vs S | NE NE 0.91 (0.32, 2.58) | NE NE 0.64 (0.47, 0.87) | 32.4 28.6 0.62 (0.38, 1.02) | NE NE 0.69 (0.47, 1.00) | 31.9 30.6 0.89 (0.51, 1.57) | NE NE 0.58 (0.41, 0.83) | NE NE 0.71 (0.49, 1.03) | 33.1 24.0 0.52 (0.31, 0.86) |
m, median; NE, not estimable.
Clinical trial identification
NCT02811861.
Editorial acknowledgement
Medical writing support was provided by Oxford PharmaGenesis Inc., Newtown, PA, USA, and was funded by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
T.K. Choueiri: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: Calithera; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Infinity; Financial Interests, Personal, Advisory Board: Surface Oncology; Financial Interests, Personal, Other, Consultant: Analysis Group; Financial Interests, Personal, Invited Speaker: Peerview; Financial Interests, Personal, Invited Speaker: PER; Financial Interests, Personal, Invited Speaker: ResearchToPractice; Financial Interests, Personal, Invited Speaker: NAMC; Financial Interests, Personal, Invited Speaker: ASCO-SITC; Financial Interests, Personal, Other, Grant to review Orien Network: ORIEN; Financial Interests, Personal, Advisory Board: Aptitude Health; Financial Interests, Personal, Invited Speaker: Advent Health; Financial Interests, Personal, Invited Speaker: UAE Society of Onc; Financial Interests, Personal, Invited Speaker: NJH Life Sciences; Financial Interests, Personal, Invited Speaker: MDACC; Financial Interests, Personal, Invited Speaker: Cancernet; Financial Interests, Personal, Invited Speaker: France Foundation; Financial Interests, Personal, Stocks/Shares: Pionyr; Financial Interests, Personal, Stocks/Shares: Tempest; Financial Interests, Personal, Invited Speaker: Springer; Financial Interests, Personal, Invited Speaker: WebMed; Financial Interests, Personal, Invited Speaker: ASiM, CE; Financial Interests, Personal, Invited Speaker: Caribou Publishing; Financial Interests, Personal, Invited Speaker: Kidney Cancer Association; Financial Interests, Personal, Royalties: Up-To-Date; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Exelixis; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: EMD-Serono; Financial Interests, Institutional, Funding: Takeda; Financial Interests, Institutional, Funding: Tracon; Financial Interests, Institutional, Funding: Peloton; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Surface Oncology; Financial Interests, Institutional, Funding: Eisai; Financial Interests, Institutional, Funding: GSK; Financial Interests, Institutional, Funding: Alliance Cooperative Group; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Leadership Role: Kidney Cancer Research Summit of Kidney Caner; Non-Financial Interests, Personal, Other: ASCO; Non-Financial Interests, Personal, Other: ESMO; Non-Financial Interests, Institutional, Other: Foundation Med; Non-Financial Interests, Institutional, Other: Guardant; Non-Financial Interests, Institutional, Other: Invitae; Non-Financial Interests, Personal, Ownership Interest: AACR; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member: AACR. M. Eto: Financial Interests, Personal, Speaker’s Bureau: Ono; Financial Interests, Personal, Speaker’s Bureau: Takeda; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Johnson & Johnson; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Chugai; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Ono; Financial Interests, Institutional, Research Grant: Takeda. S.Y. Rha: Financial Interests, Personal, Advisory Role: MSD Oncology; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Indivumed; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Research Grant: MSD Oncology; Financial Interests, Personal, Research Grant: Bristol-Myers Squibb; Financial Interests, Personal, Research Grant: Eisai; Financial Interests, Personal, Research Grant: Roche/Genentech; Financial Interests, Personal, Research Grant: MedPacto; Financial Interests, Personal, Research Grant: ASLAN Pharmaceuticals; Financial Interests, Personal, Research Grant: Sillajen; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: Immunomet. C.G. Porta: Financial Interests, Personal, Invited Speaker: Angelini-Farma; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: EUSA Pharma; Financial Interests, Personal, Invited Speaker: General Electric; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Expert Testimony: EUSA Pharma; Financial Interests, Personal, Expert Testimony: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Angelini-Farma; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Speaker’s Bureau: EUSA Pharma; Financial Interests, Personal, Speaker’s Bureau: Ipsen; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Advisory Board: Angelini-Farma; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: EUSA Pharma; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Sponsor/Funding. Roche; Financial Interests, Personal, Advisory Role: Angelini-Farma; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: EUSA Pharma; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Leadership Role: BMS; Financial Interests, Leadership Role: Eisai; Financial Interests, Leadership Role: EUSA Pharma. R. 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: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb; Financial Interests, Institutional, Principal Investigator: Eisai; Financial Interests, Institutional, Principal Investigator: Exelixis; Financial Interests, Institutional, Principal Investigator: Genetech/Roche; Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Institutional, Principal Investigator: Pfizer. V. Grünwald: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: EUSAPharm; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Janssen-Cilag; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Nanobiotix; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Stocks/Shares: AstraZeneca; Financial Interests, Personal, Stocks/Shares: BMS; Financial Interests, Personal, Stocks/Shares: MSD; Financial Interests, Personal, Stocks/Shares: Seattle Genetics; Non-Financial Interests, Other, Steering Committee Member: BMS; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Other, Steering Committee Member: Eisai; Non-Financial Interests, Institutional, Other, Steering Committee Member: Ipsen; Financial Interests, Personal and Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Personal and Institutional, Other, Steering Committee Member: Novartis; Non-Financial Interests, Research Grant: Pfizer; Non-Financial Interests, Other, Trial Chair: PharmaMar; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Advisory Role: German Cancer Society; Non-Financial Interests, Member: German Medical Oncology and Hematology Society; Non-Financial Interests, Leadership Role: Working Group Medical Oncology. T.E. Hutson: Financial Interests, Personal, Advisory Role: Bayer/Onyx; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Johnson & Johnson; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Exelixis; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Johnson & Johnson; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Speaker’s Bureau: Exelixis; Financial Interests, Personal, Speaker’s Bureau: Astellas Pharma; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Astellas Pharma; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Exelixis; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Johnson & Johnson; Financial Interests, Personal, Other, Honoraria: Bayer/Onyx; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Johnson & Johnson; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb. M.J. Méndez-Vidal: Financial Interests, Personal, Advisory Role: Janssen-Cilag; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: EUSA Pharma; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Janssen-Cilad; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Astellas Pharma; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Other, Honoraria: Astellas Pharma; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Ipsen. E. Winquist: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Other, Clinical Trail Grant-in-Aid: Canadian Cancer Trials Group; Financial Interests, Institutional, Other, Clinical Trail Grant-in-Aid: Eisai; Financial Interests, Institutional, Other, Clinical Trail Grant-in-Aid: GlaxoSmithKline; Financial Interests, Institutional, Other, Clinical Trail Grant-in-Aid: Merck; Financial Interests, Institutional, Other, Clinical Trail Grant-in-Aid: Roche. J.C.H. Goh: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Ipsen; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Institutional, Research Grant: BeiGene; Non-Financial Interests, Institutional, Principal Investigator: Eisai; Non-Financial Interests, Institutional, Principal Investigator: MSD; Non-Financial Interests, Institutional, Principal Investigator: BMS; Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator: Janssen; Non-Financial Interests, Institutional, Principal Investigator: Pfizer. P. Maroto: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: Eisai; Financial Interests, Institutional, Principal Investigator: Janssen; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Institutional, Principal Investigator: Bayer. T. Buchler: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Writing Engagements: Bayer; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Institutional, Research Grant: Servier; Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: Exelixis; Financial Interests, Institutional, Principal Investigator: Eisai. T. Takagi: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Eisai. K. Rodriguez-Lopez: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Leadership Role: Merck; Financial Interests, Personal, Stocks/Shares: Merck. D. Xing: Financial Interests, Personal, Full or part-time Employment: Eisai. A.D. Smith: Financial Interests, Personal, Full or part-time Employment: Eisai. T. Powles: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Exelixis; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Johnson & Johnson; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Ipsen; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Exelixis; Financial Interests, Personal, Other, Honoraria: Incyte; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Seattle Genetics; Financial Interests, Personal, Other, Honoraria: Merck Serono; Financial Interests, Personal, Other, Honoraria: Astellas Pharma; Financial Interests, Personal, Other, Honoraria: Johnson & Johnson; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Exelixis; Financial Interests, Personal, Research Grant: Ipsen; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: Seattle Genetics; Financial Interests, Personal, Research Grant: Merck Serono; Financial Interests, Personal, Research Grant: Astellas Pharma; Financial Interests, Personal, Research Grant: Johnson & Johnson; Financial Interests, Personal, Research Grant: Eisai. All other authors have declared no conflicts of interest.