54: Pembrolizumab plus lenvatinib vs. nivolumab plus ipilimumab in patients with clear cell renal cell carcinoma with IMDC risk intermediate or poor: A matching adjusted indirect comparison (MAIC)

Background: Nivolumab plus ipilimumab (nivo/ipi) and pembrolizumab plus lenvatinib (pem/len) have been approved and available for patients in first-line metastatic clear cell renal cell carcinoma (ccRCC). There is no direct evidence of the relative efficacy between pem/len and nivo/ipi from head-to-head clinical trials. Therefore, we conducted MAIC to better inform clinical decision-making on treatment choices.

Methods: Individual patient data with IMDC risk intermediate+poor from KEYNOTE-581 (pem/len vs. sunitinib; 50.1 months median follow-up) were compared to published aggregated data in the same IMDC risk group from CheckMate-214 (nivo/ipi vs. sunitinib; 55.5 months median follow-up). Efficacy outcomes compared were overall survival (OS), progression free survival (PFS), and objective response rate (ORR). Effect modifiers identified included liver/bone metastasis, and IMDC risk category. Using MAIC, KEYNOTE-581 data were reweighted to match the effect modifiers distribution of CheckMate-214 participants. Then, matching-adjusted hazard ratios (HR) for OS and PFS, and risk difference (RD) for ORR of pem/len vs. sunitinib were calculated using the reweighted KEYNOTE-581 data. Bucher method was subsequently applied to indirectly compare pem/len to nivo/ipi on these outcomes. Two-sided p-values were calculated.

Results: MAIC analyses show that, while OS were comparable between treatments (HR: 1.09 [95% CI:0.79-1.51]; p=0.5939), pem/len significantly improved PFS (HR: 0.55 [95% CI:0.41-0.75]; p=0.0002) and ORR (RD: 29.60 [95% CI:19.27-39.93]; p< 0.001) when compared to nivo/ipi.

Conclusions: In first-line metastatic ccRCC patients with IMDC risk intermediate+poor, MAIC shows that pembrolizumab plus lenvatinib demonstrated clinical advantages against nivolumab plus ipilimumab on PFS and ORR, and a comparable OS benefit.