Risky business.
Top line: There’s been a whole lotta trials on systemic therapy for advanced renal cell carcinoma (RCC) over the past year. Are there any clear winners?
The Study: Results of the Checkmate 214 trial were published last week, and it’s looking to place combo nivo + ipi on the throne. Over 1K patients with untreated advanced RCC were enrolled and stratified by IDMC risk then randomized to the experimental combo of nivolumab + ipilimumab versus the long time standard of sunitinib alone. They got a little greedy with *three* co-primary endpoints of objective response (OR, 𝝰 of 0.001), progression free survival (PFS, 𝝰 of 0.009) and overall survival (OS, 𝝰 of 0.04) rates specifically among the intermediate/high risk (I/HR) patients (n=839), with exploratory analyses performed on the remaining low risk (LR) patients (n=223). At 18 months, rates of OR (27 → 42%) and OS (60 → 75%) among the I/HR patients were significantly improved with combo nivo + ipi. Median PFS was also improved (8 → 11 months) but not significantly given such little 𝝰 to work with. As expected, survival among the LR patients was excellent (>95% at one year), but, surprisingly, OR at 18 months (52 → 29%) and median PFS (25 → 15 months) were significantly worse with combo nivo + ipi. Huh.
Bottom Line: Combo nivo + ipi has dethroned sunitinib as first-line systemic therapy for intermediate/high risk advanced RCC, but don’t be too quick to extrapolate to low risk patients. | Motzer, N Engl J Med 2018
The Study: Results of the Checkmate 214 trial were published last week, and it’s looking to place combo nivo + ipi on the throne. Over 1K patients with untreated advanced RCC were enrolled and stratified by IDMC risk then randomized to the experimental combo of nivolumab + ipilimumab versus the long time standard of sunitinib alone. They got a little greedy with *three* co-primary endpoints of objective response (OR, 𝝰 of 0.001), progression free survival (PFS, 𝝰 of 0.009) and overall survival (OS, 𝝰 of 0.04) rates specifically among the intermediate/high risk (I/HR) patients (n=839), with exploratory analyses performed on the remaining low risk (LR) patients (n=223). At 18 months, rates of OR (27 → 42%) and OS (60 → 75%) among the I/HR patients were significantly improved with combo nivo + ipi. Median PFS was also improved (8 → 11 months) but not significantly given such little 𝝰 to work with. As expected, survival among the LR patients was excellent (>95% at one year), but, surprisingly, OR at 18 months (52 → 29%) and median PFS (25 → 15 months) were significantly worse with combo nivo + ipi. Huh.
Bottom Line: Combo nivo + ipi has dethroned sunitinib as first-line systemic therapy for intermediate/high risk advanced RCC, but don’t be too quick to extrapolate to low risk patients. | Motzer, N Engl J Med 2018
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