1BA The impact of pathological factors on long-term local control in the EORTC boost no-boost trial

patients (pts) with advanced renal cell carcinoma (RCC), treatment with cabozantinib was associated with encouraging clinical activity. The objective of the METEOR trial was to evaluate the efficacy and safety of cabozantinib compared to everolimus in pts with clear cell RCC and disease progression following treatment with one or more VEGFR tyrosine kinase inhibitors (TKIs). Methods: In this open-label phase 3 trial (NCT01865747), pts were randomized 1:1 to receive cabozantinib (60mg QD) or everolimus (10mg QD). Pts had measurable disease per RECIST 1.1, KPS 70%, and were stratified by MSKCC prognostic criteria and number of prior VEGFR TKIs. Patients must have progressed within 6 months of their prior VEGFR TKI. The primary endpoint was progression-free survival (PFS) per independent radiology committee (IRC). The trial was designed for an event-driven analysis of PFS events among the first 375 randomized pts to provide 90% power to detect a hazard ratio of 0.667 with a 2-sided 0.05 level of significance using a stratified log-rank test. Secondary efficacy endpoints include objective response rate (ORR) and overall survival (OS) among all randomized pts. Results: A total of 658 pts were randomized between Aug 2013 and Nov 2014. 71% pts had 1 and 29% pts 2 or more prior VEGFR TKIs. 46% pts were favorable, 41% intermediate, and 13% poor risk by MSKCC criteria. The study met the primary endpoint. The estimated median PFS among the first 375 randomized pts was 7.4 months for pts receiving cabozantinib, and 3.8 months for patients receiving everolimus, HR 0.58 (95% CI 0.45 to 0.75), p < 0.001. Prespecified subgroup analyses for PFS will be presented. The ORR in the PFS population was 21% with cabozantinib compared to 5% with everolimus (P < 0.001). At the interim analysis of OS (49% information fraction) among all 658 pts, the hazard ratio was 0.67 (95% CI 0.51 to 0.89), p = 0.0050, in favor of cabozantinib, not meeting the criteria for early rejection of H0 (p 0.0019). Medians for OS could not yet be estimated. The most common serious adverse events for pts receiving cabozantinib were abdominal pain (3%), pleural effusion (2.7%), diarrhoea (2.1%), and for pts receiving everolimus were anemia (3.7%), dyspnoea (3.7%), pneumonia (3.7%). Treatment discontinuation for adverse events occurred in 9.1% for cabozantinib and 10% for everolimus. Conclusions: Cabozantinib demonstrated improvement in PFS and ORR compared with everolimus in VEGFR TKI pretreated pts with advanced clear cell RCC. A trend of improved survival for pts receiving cabozantinib was observed at the interim analysis. The incidence of serious adverse events was similar in both arms. Conflict of interest: Ownership: Stock ownership: Anne Borgman-Hagey, Colin Hessel, Christian Scheffold, Gisela Schwab. Advisory Board: Tannir, Powles, Escudier. Corporate-sponsored Research:. Tannir, Roth, Motzer, Heng, Hammers, Choueiri. Other Substantive Relationships: Honoraria: Tannir, Escudier.