High tumor burden (TB) in pts with RCC is associated with poor prognosis (Iacovelli BJU Int 2012). In the Phase 3 METEOR trial (NCT01865747) in advanced RCC after prior vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) therapy (Choueiri NEJM 2015/ASCO 2016 abstr 4506), cabo significantly improved progression-free survival (PFS; HR 0.58, 95% CI 0.45–0.74; P
658 pts were randomized 1:1 to cabo (60 mg qd) or eve (10 mg qd). Stratification factors were MSKCC risk group and number of prior VEGFR TKIs. Endpoints included PFS, OS and ORR. Subgroup analyses by metastatic site and low and high TB (< median and ≥ median sum of target lesion diameters [SoD] at baseline) are presented.
At baseline, 74% of pts had visceral (lung or liver) metastases (mets); 63% had lung mets and 29% had liver mets. Median SoD at baseline was 65 mm (range 0–291) in the cabo arm and 65 mm (0–258) in the eve arm. Subgroups by metastatic site and TB generally had similar baseline characteristics on both arms. High compared to low TB was associated with fewer favorable (34% vs 57%) and more intermediate (47% vs 36%) and poor risk (19% vs 7%) pts per MSKCC criteria. For pts with visceral mets, the HRs favored cabo (PFS HR 0.48, 95% CI 0.38–0.60; OS HR 0.66, 95% CI 0.52–0.85). These benefits with cabo were consistent across the metastatic sites analyzed (liver and lung). For pts with low TB, HRs for cabo vs eve were 0.63 (95% CI 0.47–0.84) for PFS and 0.76 (95% CI 0.54–1.08) for OS vs 0.41 (95% CI 0.31–0.54) for PFS and 0.60 (95% CI 0.45–0.80) for OS for pts with high TB. Median OS with cabo was 22.0 mo for low TB and 18.1 mo for high TB pts vs 19.3 mo and 12.2 mo with eve, respectively. The most common grade 3 or 4 adverse events in these subgroups were consistent with the safety profile in the overall study population.
Treatment with cabo was associated with improved PFS and OS compared to eve in pts irrespective of tumor burden or metastatic sites. Pts with high tumor burden appeared to have a stronger relative benefit with cabo compared to eve for both OS and PFS.
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T.B. Powles: Honoraria- Roche, Genentech, Novartis Consulting/Advisory- Roche, Genentech, Bristol Meyers Squibb Research Funding- AZ/Medimmune, Roche, Genentech, GlaxoSmithKline B. Escudier: Honoraria- Exelixis, Novartis, Pfizer, BMS, Roche. S. Chowdhury: Membership on an advisory board or board of directors: Sanofi, Astellas, Novartis, Janssen, Bayer, Essa, Pfizer, Clovis, Corporate-sponsored research or other substantive relationships:Sanofi, Astellas. D. Pook: Travel, Accommodations, Expenses - Astellas, Pfizer, Novartis. U. Harmenberg: Leadership- Medivir, Oncopeptides, Glionova Stock Ownership-Medivir, Ahihion. N. Basappa: Honoraria -Astellas, Janssen, Pfizer, Novartis, BMS Consulting Role- Research Funding - Lilly, Agensys, Amgen, Bayer, BI. D. Geynisman: Consulting and Advisory Role- Pfizer, Novartis, Prometheus Research Funding - Pfizer J. Merchan: Research Funding - Exelixis, Agensys, Rexaham, Eli Lilly. C. Ryan: Research Funding- Janssen, MabVax, Morphotek, OSI, Threshold, Argos, BMS, CytRx, Eisai, Exelixis, GSK, Consulting and Advisory Role- Karyopharm, EMD-Serono, Eisai, Pfizer, Onyx, Janssen O. Goodman: Honoraria - Medivation Consultancy/Advisory Role- Medivation, Exelixis Speakers Bureau – Medivation. P. Singh: Consulting and Advisory Role- Prometheus, Genentech Speakers' Bureau - Genentech J. Lougheed, M. Patel: Employment and Stock – Exelixis. J.J. Knox: Research Funding - Pfizer, Astra Zeneca Consulting and Advisory Role – Cellgene. R.J. Motzer: Consulting Advisory Role- Exelixis, Novartis, Eisai, Inc 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. All other authors have declared no conflicts of interest.