1698P - Avelumab + axitinib (Ave + Axi) vs sunitinib (Sun) in advanced renal cell carcinoma (aRCC): Final analysis of patient (pt)-reported outcomes (PROs) and quality-adjusted time without symptoms or toxicity (Q-TWiST)

Background

The JAVELIN Renal 101 phase 3 trial (NCT02684006) showed improved progression-free survival (PFS) and tumor responses with first-line Ave + Axi vs Sun treatment in pts with aRCC, with an acceptable safety profile. We report analyses of PROs and Q-TWiST, an integrated measure incorporating efficacy, safety, and PROs into a single value to assess quantity and quality of survival.

Methods

PROs (secondary endpoint) were assessed using 2 validated instruments: EQ-5D-5L and FKSI-19. In a post hoc exploratory analysis of Q-TWiST, overall survival (OS) in each arm during the analysis period (72 months from randomization) was partitioned into 3 health states: time with all-cause grade ≥3 toxicity prior to progression (TOX), time without toxicity or symptoms of disease progression (TWiST), and survival after progression (relapse; REL). Q-TWiST was calculated by summing restricted mean time in each health state after adjustment for utility weights based on EQ-5D-5L index scores.

Results

Completion rates for PRO instruments during treatment were >90% at almost all time points in both arms. PRO scores were similar for Ave + Axi vs Sun and remained relatively stable over time. Among treated pts, time in TOX and TWiST was longer with Ave + Axi vs Sun, whereas time in REL was shorter with Ave + Axi because pts had more time in the progression-free state, resulting in less time in REL (table). Ave + Axi treatment resulted in a 3.20-month gain in Q-TWiST vs Sun (10.9% relative improvement; established clinically important difference ≥10%).

Conclusions

PRO results indicate that Ave + Axi combination treatment had no adverse impact on health-related quality of life vs Sun monotherapy in pts with aRCC. Q-TWiST was longer with Ave + Axi vs Sun, showing that Ave + Axi treatment provides an increase in quality-adjusted survival time vs Sun. Table: 1698P

Clinical trial identification

NCT02684006, first posted February 17, 2016.

Editorial acknowledgement

Medical writing support was provided by Katherine Quiroz-Figueroa of Nucleus Global and was funded by Merck.

Legal entity responsible for the study

Merck as part of a previous alliance between Merck and Pfizer.

Funding

This trial was sponsored by Pfizer and was previously conducted under an alliance between Merck (CrossRef Funder ID: 10.13039/100009945) and Pfizer. This analysis was sponsored by Merck.

Disclosure

B. Venugopal: Financial Interests, Personal, Advisory Role: Ipsen, Merck, MSD, Pfizer; Financial Interests, Personal, Speaker, Consultant, Advisor: Eisai Limited, EUSA Pharma, Ipsen, MSD; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, Eisai Limited, EUSA Pharma, Pfizer; Financial Interests, Personal, Research Funding: Calithera Biosciences, Merck, MSD, Pfizer. T.K. Choueiri: Financial Interests, Personal and Institutional, Research Funding: Aravive, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Circle Pharma, CME events (PeerView, OncLive, MJH, and others), Eisai, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Exelixis, GSK, IQVIA, Infinity, Ipsen, Jansen, Kanaph, Lilly, MSD, Nikang, Novartis, Nuscan, Pfizer, Roche, Sanofi/Aventis, Surface Oncology, Takeda, Tempest, Up-To-Date; Financial Interests, Personal and Institutional, Advisory Board: Aravive, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Circle Pharma, CME events (PeerView, OncLive, MJH, and others), Eisai, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Exelixis, GSK, IQVIA, Infinity, Ipsen, Jansen, Kanaph, Lilly, MSD, Nikang, Novartis, Nuscan, Pfizer, Roche, Sanofi/Aventis, Surface Oncology, Takeda, Tempest, Up-To-Date; Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: Aravive, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Circle Pharma, CME events (PeerView, OncLive, MJH, and others), Eisai, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Exelixis, GSK, IQVIA, Infinity, Ipsen, Jansen, Kanaph, Lilly, MSD, Nikang, Novartis, Nuscan, Pfizer, Roche, Sanofi/Aventis, Surface Oncology, Takeda, Tempest, Up-To-Date; Financial Interests, Personal and Institutional, Other, Honoraria: Aravive, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Circle Pharma, CME events (PeerView, OncLive, MJH, and others), Eisai, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Exelixis, GSK, IQVIA, Infinity, Ipsen, Jansen, Kanaph, Lilly, MSD, Nikang, Novartis, Nuscan, Pfizer, Roche, Sanofi/Aventis, Surface Oncology, Takeda, Tempest, Up-To-Date; Financial Interests, Personal, Other, Equity: Osel, Pionyr, Precede Bio, Tempest; Financial Interests, Personal, Steering Committee Member: ACCRU, ASCO, ESMO, GU Steering Committee, KidneyCan, NCCN; Financial Interests, Institutional, Funding: Dana-Farber Cancer Institute; Financial Interests, Institutional, Royalties: Dana-Farber Cancer Institute; Financial Interests, Personal, Financially compensated role: Dana-Farber/Harvard Cancer Center Kidney SPORE (2P50CA101942-16) and Program 5P30CA006516-56, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, Pan Mass Challenge, Loker Pinard Funds for Kidney Cancer Research at DFCI. K.D. Penkov: Financial Interests, Personal, Other, Honoraria: AstraZeneca, MSD, Nektar, Pfizer, Regeneron, Roche; Financial Interests, Personal, Advisory Role: Nektar. L. Albiges: Financial Interests, Institutional, Other, Consulting: Astellas, BMS, Eisai, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche, Merck, Amgen; Financial Interests, Personal, Other, Honoraria: Novartis; Non-Financial Interests, Principal Investigator, Clinical trial steering committee: Pfizer, BMS, AVEO, AstraZeneca, MSD; Non-Financial Interests, Principal Investigator: Ipsen; Non-Financial Interests, Other, Clinical trial steering committee: Roche, Exelixis; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Other, Medical Steering Committee: Kidney Cancer Association; Non-Financial Interests, Other, Member of the Renal Cell Carcinoma Guidelines Panel: European Association of Urology (EAU). H. Uemura: Financial Interests, Personal, Speaker, Consultant, Advisor: Bayer, Bristol Myers Squibb, Janssen, MSD, Pfizer; Financial Interests, Personal, Research Funding: Astellas, AstraZeneca, Daiichi Sankyo, Janssen, Kissei, Ono, Sanofi, Takeda. J. Larkin: Financial Interests, Personal, Advisory Role: Achilles Therapeutics, AstraZeneca, Bristol Myers Squibb, BioNTech, CureVac, Eisai, Imcyse, Immunocore, Instil Bio, Iovance Bio, Ipsen, Molecular Partners, MSD, Neogene Therapeutics, Novartis, Pfizer, PokeAcell, Roche/Genentech, Sanofi, Sastra Cell Therapy, Scenic, Seagen, Third Rock Ventures, T-Knife; Financial Interests, Personal, Research Funding: Amgen, Asher Bio, Bristol Myers Squibb, MSD, Neon Therapeutics, Novartis, Sastra Cell Therapy. Y. Tomita: Financial Interests, Personal, Advisory Role: Novartis, Ono Pharmaceutical, Taiho Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Astellas Pharma, Bristol Myers Squibb, Chugai Pharma, Novartis, Ono Pharmaceutical, Pfizer, Merck, MSD; Financial Interests, Institutional, Research Funding: Astellas Pharma, AstraZeneca, Chugai Pharma, Eisai, MSD, Novartis, Ono Pharmaceutical, Pfizer, Takeda. J. Wang: Financial Interests, Full or part-time Employment: Pfizer; Financial Interests, Stocks or ownership: Pfizer. J. Hoffman: Financial Interests, Personal, Full or part-time Employment: EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA; Financial Interests, Personal, Stocks or ownership: Merck, MSD, Pfizer. A. Gerhold-Ay: Financial Interests, Personal, Full or part-time Employment: Merck. P. Kieslich: Financial Interests, Personal, Full or part-time Employment: Merck. R.J. Motzer: Financial Interests, Personal, Advisory Role: AstraZeneca, Aveo, Calithera Biosciences, Eisai, Exelixis, Genentech/Roche, Incyte, Merck, Pfizer; Financial Interests, Personal, Other, Travel, accommodations, and expenses: Bristol Myers Squibb; Financial Interests, Personal, Research Funding: Aveo, Bristol Myers Squibb, Eisai, Exelixis, Genentech/Roche, Novartis, Merck, Pfizer.