METEOR
A Study of Cabozantinib (XL184) vs Everolimus in Subjects With Metastatic Renal Cell Carcinoma
Phase 3N = 658NCT01865747
- Population
- Advanced renal cell carcinoma that progressed after VEGFR-targeted therapy
- Design
- Open-label randomised (1:1) phase 3 trial of cabozantinib 60 mg daily versus everolimus 10 mg daily in advanced or metastatic clear-cell renal cell carcinoma with measurable disease and previous treatment with one or more VEGFR tyrosine-kinase inhibitors. Stratified by MSKCC risk group and number of previous VEGFR TKIs. Primary end point progression-free survival by independent radiology review; secondary end points overall survival and objective response.
- Primary endpoint
- PFS
- Arms
- Cabozantinib (experimental, n = 330): Cabozantinib 60 mg orally once daily
- Everolimus (control, n = 328): Everolimus 10 mg orally once daily
- People
- Choueiri TK, METEOR Investigators
PFSHR 0.58 (95% CI 0.45–0.75)Δ median PFS+3.6 monthsΔ ORR+16 pointsOSHR 0.67 (95% CI 0.51–0.89)OSHR 0.66 (95% CI 0.53–0.83)Δ median OS+4.9 months
Show the numbers
| Endpoint | Analysis | Cabozantinib | Everolimus | Effect |
|---|---|---|---|---|
| PFSPFS population: first 375 randomised patients (187 cabozantinib, 188 everolimus); intention-to-treat principle; independent radiology review | primaryChoueiri 2015 | median 7.4 months | median 3.8 months | HR 0.58 (95% CI 0.45–0.75)P<0.001Primary PFS analysis in the first 375 randomly assigned patients (NEJM full text, PMC5024539; also stated in the Lancet Oncology abstract); the NEJM abstract itself does not say which patients this median and hazard ratio cover. |
| ORRFirst 375 randomised patients (PFS population), independent review | primaryChoueiri 2015 | 21% | 5% | P<0.001The NEJM full text reports the 21% versus 5% objective response (partial responses) in the first 375 randomised patients. |
| OSOverall survival population: all 658 randomised patients (202 deaths at the prespecified interim analysis) | interimChoueiri 2015 | — | — | HR 0.67 (95% CI 0.51–0.89)P=0.005Planned interim analysis; the abstract states the result did not cross the significance boundary for the interim analysis. |
| OSITT (all randomly assigned patients) | finalChoueiri 2016 | median 21.4 months | median 16.5 months (14.7–18.8) | HR 0.66 (95% CI 0.53–0.83)P=0.00026The paper's title calls this the final overall survival result, and its abstract says it is based on an unplanned second interim analysis; the NEJM full text had planned the final analysis after 408 deaths. The 95% confidence interval of the cabozantinib median is printed as 18.7 to not estimable and is not recorded as a numeric interval. Median follow-up for overall survival and safety was 18.7 months (cabozantinib) and 18.8 months (everolimus). |
| PFSAll randomly assigned patients, independent radiology review | finalChoueiri 2016 | — | — | HR 0.51 (95% CI 0.41–0.62)P<0.0001Progression-free survival among all randomised patients per independent radiology review. |
| ORRAll randomly assigned patients, independent radiology review | finalChoueiri 2016 | 17% (13–22%) | 3% (2–6%) | P<0.0001 |
| Endpoint | Analysis | Cabozantinib | Everolimus | Effect |
|---|---|---|---|---|
| PFSPFS population: first 375 randomised patients (187 cabozantinib, 188 everolimus); intention-to-treat principle; independent radiology review | primaryChoueiri 2015 | median 7.4 months | median 3.8 months | HR 0.58 (95% CI 0.45–0.75)P<0.001Primary PFS analysis in the first 375 randomly assigned patients (NEJM full text, PMC5024539; also stated in the Lancet Oncology abstract); the NEJM abstract itself does not say which patients this median and hazard ratio cover. |
| ORRFirst 375 randomised patients (PFS population), independent review | primaryChoueiri 2015 | 21% | 5% | P<0.001The NEJM full text reports the 21% versus 5% objective response (partial responses) in the first 375 randomised patients. |
| OSOverall survival population: all 658 randomised patients (202 deaths at the prespecified interim analysis) | interimChoueiri 2015 | — | — | HR 0.67 (95% CI 0.51–0.89)P=0.005Planned interim analysis; the abstract states the result did not cross the significance boundary for the interim analysis. |
| OSITT (all randomly assigned patients) | finalChoueiri 2016 | median 21.4 months | median 16.5 months (14.7–18.8) | HR 0.66 (95% CI 0.53–0.83)P=0.00026The paper's title calls this the final overall survival result, and its abstract says it is based on an unplanned second interim analysis; the NEJM full text had planned the final analysis after 408 deaths. The 95% confidence interval of the cabozantinib median is printed as 18.7 to not estimable and is not recorded as a numeric interval. Median follow-up for overall survival and safety was 18.7 months (cabozantinib) and 18.8 months (everolimus). |
| PFSAll randomly assigned patients, independent radiology review | finalChoueiri 2016 | — | — | HR 0.51 (95% CI 0.41–0.62)P<0.0001Progression-free survival among all randomised patients per independent radiology review. |
| ORRAll randomly assigned patients, independent radiology review | finalChoueiri 2016 | 17% (13–22%) | 3% (2–6%) | P<0.0001 |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.58 | 0.45–0.75 |
| OS | 0.67 | 0.51–0.89 |
| OS | 0.66 | 0.53–0.83 |
| PFS | 0.51 | 0.41–0.62 |
- Cabozantinib (experimental)
- Everolimus (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Cabozantinib | Everolimus |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 5 | 62.6% | 40.2% |
| 9 | 43.0% | 19.4% |
| 14 | 26.9% | 7.8% |
| 19 | 16.9% | 3.1% |
- Cabozantinib (experimental)
- Everolimus (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Cabozantinib | Everolimus |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 13 | 65.6% | 57.9% |
| 27 | 41.7% | 32.2% |
| 40 | 27.4% | 18.6% |
| 54 | 17.4% | 10.3% |
Appears in
Sources
Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, et al. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015;373(19):1814-23.
Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17(7):917-927.