In this 3-arm study, treatment-naïve mRCC patients were randomized to atezo + bev vs. atezo monotherapy vs. sunitinib monotherapy. PD-L1 expression was documented on immune cells prior to treatment. Primary endpoints were progression-free survival (PFS) in all patients and those who were specifically PD-L1-positive.
At follow-up, median survival was 20.7 months. The overall progression-free survival (PFS) hazard ratio for intention-to-treat atezo+bev vs. sunitinib was 1.0. The PFS hazard ratio for atezo vs. sunitinib was 1.19. As investigators expected, PD-L1+ patients hazard ratios were 0.64 for atezo+bev (46 months PFS) vs. sunitinib (27 months PFS) and 1.03 for atezo vs. sunitinib. None of these hazard ratios were statistically significant. Treatment-related Grade 3-4 AEs were seen in 40%, 16% and 57% of pts in the atezo+bev, atezo and sunitinib arms, respectively, indicating that combination therapy and atezo monotherapy are better tolerated than VEGF monotherapy. Important to note, the majority of sunitinib-only and atezo-only patients eventually received atezo+bev during the study duration. Analysis of crossover treatment is currently ongoing.
In conclusion, patients expressing PD-L1 appeared to benefit the most from atezo+bev as first-line therapy in mRCC. The combined toxicity of atezo+bev is significant (40% Grade 3-4 AEs), though still less than gold standard VEGF therapy (57%). This combination therapy is currently under Phase III investigation (IMmotion151).
This study highlights the utility of biomarkers (PD-L1 in this case) in prospective trials. Although atezo+bev appears to have beneficial effects compared to sunitinib, atezo monotherapy still appears to demonstrate activity on par with front-line sunitinib monotherapy. This adds credence to the use of checkpoint inhibitors in this space, and trials such as this will certainly lead to improved combination therapies moving forward.
First author: David F. McDermott
Written By: Shreyas Joshi, MD, Fox Chase Cancer Center
at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA