METEOR
In advanced clear-cell RCC progressing after prior VEGFR-targeted therapy, does cabozantinib improve outcomes versus everolimus—and does benefit persist after different prior agents?
Overall efficacy
| Endpoint | Cabozantinib | Everolimus |
|---|---|---|
| Median PFS | 7.4 months | 3.8 months |
| Median OS | 21.4 months | 16.5 months |
| Objective response rate | 17% | 3% |
Cabozantinib improved PFS (HR 0.58), OS (HR 0.66) and ORR compared with everolimus in the primary analysis.
Does efficacy persist after the prior first-line agent?
The METEOR subgroup analysis is clinically useful because the comparator remained everolimus even when patients had received different VEGFR TKIs previously.
| Prior VEGFR agent | Median PFS: cabo vs everolimus | Median OS: cabo vs everolimus | ORR: cabo vs everolimus |
|---|---|---|---|
| Sunitinib only (n=267) | 9.1 vs 3.7 months; HR 0.43 | 21.4 vs 16.5 months; HR 0.66 | 16% vs 3% |
| Pazopanib only (n=171) | 7.4 vs 5.1 months; HR 0.67 | 22.0 vs 17.5 months; HR 0.66 (CI crossed 1) | 19% vs 4% |
| Prior anti-PD-1/PD-L1 exposure (small subgroup, n=32) | Not reached vs 4.1 months; HR 0.22 | Not reached vs 16.3 months; HR 0.56 (wide CI) | 22% vs 0% |
Critical appraisal and harms
METEOR provides randomized evidence that changing target profile to cabozantinib can be effective after prior VEGFR inhibition; it does not imply that every VEGFR TKI is interchangeable. Cabozantinib inhibits VEGFR, MET and AXL, which may be relevant to resistance biology. Toxicities include diarrhoea, palmar-plantar erythrodysaesthesia, hypertension, fatigue and dose reductions; everolimus has a different profile including stomatitis, metabolic effects and pneumonitis.
Prior-agent subgroup analyses are not independent randomized trials; interpret confidence intervals and small subgroup sizes carefully. Do not derive subgroup NNT from median PFS or hazard ratios.
Current-practice context
In the modern first-line IO–TKI era, METEOR remains foundational evidence for cabozantinib after prior VEGFR-targeted therapy, but it predates widespread first-line ICI combinations. It supports cabozantinib as an active later-line option; CONTACT-03 and TiNivo-2 separately address the question of adding/rechallenging ICI after prior ICI progression and did not support routine ICI rechallenge.
Dated context added 14 October 2026; comprehensive guideline reconciliation remains ongoing.