In a randomized Phase 3 trial in advanced RCC after prior VEGFR TKI therapy (Choueiri N Engl J Med 2015, ASCO 2016 abstract 4506) cabozantinib was superior to everolimus in the primary endpoint of PFS (median 7.4 vs 3.8 mo; HR 0.58; p
658 patients were randomized 1:1 to receive cabozantinib 60 mg qd (n = 330), or everolimus 10 mg qd (n = 328). QoL questionnaires (Functional Assessment of Cancer Therapy-Kidney Symptom Index [FKSI-19] and EuroQol EQ-5D-5L) were administered on Day 1 (pre-dose), every 4 weeks through W25D1, then every 8 weeks through final tumor assessment. The FKSI-19 has 19 items each scored on a 5-point scale (0-4); a 9-item disease-related symptom index (FKSI-DRS) is a subset. Higher scores indicate better QoL. A priori statistical methods included a repeated-measures mixed-effects model change from baseline (BL) analysis. An important change was defined as an effect size (ES) ≥ 0.3.
Completion rates were ≥ 75% of patients (# completed/expected at each timepoint) through Week 48 for both instruments. The FKSI-19 total score was similarly sustained in each arm over time: estimated mean change from BL −3.48 cabozantinib vs −2.21 everolimus (ES difference −0.13). Scores at end of treatment (mainly due to progression) were ∼7 points lower than BL in each arm. On the Treatment Side Effects subscale, diarrhea and nausea were worse for cabozantinib (ES -0.77 and -0.34, respectively), shortness of breath was worse for everolimus (ES +0.30). Diarrhea and nausea are frequent AEs for VEGFR TKIs. No treatment differences were observed for the other three FKSI subscales (DRS-Physical, DRS-Emotional, Function/Well Being) or for the EQ-5D-5L questionnaire. In a post hoc analysis, median time to deterioration (earlier of death, progression, or ≥ 4-point decrease in FKSI-DRS) was longer in the cabozantinib arm (5.5 vs 3.7 mo; p
Cabozantinib improved PFS, OS, and ORR, and resulted in QoL similar to everolimus in patients with advanced RCC. The benefits of cabozantinib are further supported by a delay of time to deterioration.
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D. Cella: Stock or Other Ownership: Facit.org Patents, Royalties, Other Intellectual Prop.: Facit.org B. Escudier: Honoraria: Exelixis, Novartis, Pfizer, BMS, Roche. N. Tannir: Honoraria: Novartis, BMS, GSK, Pfizer, Exelixis, Nektar Consulting Fees: Novartis, BMS, GSK, Pfizer, Exelixis, Nektar Research Funding: Novartis, BMS, Exelixis, Epizyme Travel, Accomodations, Expenses: Novartis, BMS, GSK, Pfizer, Exelixis, Nektar. T. Powles: Honoraria: Roche/Genentech, Novartis Consulting or Advisory Role: Roche/Genentech, BMS Research Funding: AZ/MedImmune, Roche/Genentech, GSK. F. Donskov: Research Funding: Novartis, GSK, Pfizer (received by institution). K. Peltola: Employee: Part-time, Orion Pharma Stock/other Ownership: Faron Pharma Honoraria: Novartis, Lilly Consulting/Advisory: Lilly, BMS, Sanofi, Baxter, Pfizer, MSD, Astellas. Travel Accomodations: Pierre Fabre, BMS, Novartis, Lilly. M. Schmidinger: Honoraria: Pfizer, Roche, BMS, Novartis Consulting/Advisory: Pfizer, Roche, BMS, Novartis, Exelixis Research Funding: Pfizer, Roche. D. Heng: Consulting/Advisory: Pfizer, Novartis, BMS, Exelixis. P. Mainwaring: Honoraria, Consulting/Advisory, Speakers' Bureau: Astellas, Janssen, Roche, Novartis Patents, Royalties, Other Intellectual Prop: Xing Technologies P/L Travel Accomodations: Astellas, Janssen, Roche. H. Hammers: Research Funding: sfj, BMS, Newlink, Pfizer, GSK, Tracon Consulting/Advisory: BMS, Exelixis, Pfizer, Cerulean. J-L. Lee: Honoraria: Pfizer, Astellas, Novartis Consulting/Advisory: AZ Research Funding: Pfizer, Bayer, Novartis, Exelixis, MSD, Roche, AZ. B.I. Rini: Research Funding: Pfizer, BMS, Peleton, Acceleron, Furmatics Consulting/Advisory: Pfizer, Roche, BMS, Acceleron, Novartis, GSK Travel Accomodations, Expenses: Pfizer. B. Roth: Research Funding: Argos, Medivation, Exelixis, Jansen. J. Baer: Employment: Exlexis Stock or other ownership: Exelixis, GSK. M. Mangeshkar: Employee and Stock Ownership: Exelixis, Inc. C. Scheffold: Employee: Exelixis Stock or other ownership: Exelixis. T. Hutson: Research Funding: Pfizer, Bayer, BMS, Novartis Honoraria: Pfizer, Novartis, Bayer, BMS Consulting/Advisory: Pfizer, Novartis, Bayer, Exelixis, Eisai, BMS Speakers' Bureau: Pfizer, Novartis, Bayer, BMS. S. Pal: honoraria: Novartis, Medivation, Astellas Pharma consulting fees: Pfizer, Novartis, Aveo, Genentech, Exelixis, BMS, Astellas, GSK. R.J. Motzer: Consulting/Advisory: Pfizer, Novartis, Eisai Research Funding: Exelixis, BMS, Novartis, Pfizer, Genentech/Roche. T.K. Choueiri: Consulting/Advisory Role: Pfizer, GSK, Novartis, Merck, Bayer, Eisai, Roche, Prometheus Labs Inc, BMS, Foundation Medicine Inc. Research Funding: Pfizer, GSK, Novartis, BMS, Merck, Exelixis, Roche, AstraZeneca, Tracon, Peloton.