Bristol and Exelixis score in kidney cancer, but will it be enough?

Another unequivocally positive study of a PD-1-VEGF combination in kidney cancer presents oncologists with a problem they probably consider themselves fortunate to have: which regimen to choose? Following Keytruda plus Inlyta and Bavencio plus Inlyta, Bristol-Myers Squibb and Exelixis today unveiled topline data from Checkmate-9ER, a trial of Opdivo and Cabometyx; impressive hazard ratios were detailed for progression-free and overall survival. Of course, the real competition here is Keytruda, which in Keynote-426 blew previous studies out the water; until a full readout of Checkmate-9ER is available it is hard to know how effectively Bristol and Exelixis might compete. A cross-trial comparison, with the usual caveats, suggests that the game is still on. Keynote-426 generated very impressive responses at interim readout, though later cuts of the data showed a very similar reduction in the risk of death to the 9ER result. On progression-free survival it is the Opdivo combination that appears to have an edge, although again the numbers behind this result need to be known. Still, the Keytruda/Inlyta combo has been available in this setting since April 2019, and first to market might well be the most important factor for commercial success.

Battle of the hazard ratios: Merck vs Bristol in first-line kidney cancer 
  Checkmate-9ER  Keynote-426
  @18.1 mth follow-up*  @12.8 mth follow-up**  @16.6 mth follow-up***
Hazard ratio for PFS  0.51 (p<0.0001) 0.69 0.69
Median in months  ? 15.1 vs 11.0 17.1 vs 11.1 
Hazard ratio for OS  0.60 (p<0.001) 0.53 0.59
Median in months  ? NR vs NR  NR vs NR 
Sources: *company release; **data on label; ***EMA report. 

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