Cometriq will not be able to escape comparisons with Opdivo. The first blow was their near-simultaneous release of positive results in renal cell carcinoma in July, and on Saturday they were put side by side in a late-breaking data session at the European Cancer Congress in Vienna.
Not that the Exelixis kinase inhibitor had been given much of a chance; analysts have attributed a huge share of the growth in kidney cancer to the competing Bristol-Myers Squibb immuno-oncology agent. With a demonstrated overall survival benefit on Opdivo’s side to only progression-free survival so far for Cometriq, the financial community is betting that oncologists will reach for the latter first – though the lead investigator in the Cometriq trial argued that the choice was not so simple.
“The overall survival is striking with [Opdivo],” acknowledged Toni Choueiri, medical professor at Harvard University and kidney director with the Dana-Farber Cancer Institute. But he added, “These are different drugs – oral vs IV, for example – and a lot of things are going to get into the equation such as the familiarity of physicians.”
Cometriq has the misfortune of not having its data mature enough to report overall survival data, although Dr Choueiri said early findings suggested a trend towards survival. An interim look suggested a statistically significant survival hazard ratio of 0.67 in favour of Cometriq over the comparator drug Afinitor, although the follow-up is not long enough to calculate a median.
Opdivo’s survival benefit over Afinitor is more than five months – 25 vs 19.6 – a finding that will almost surely earn it an FDA approval with a strong label; Cometriq, too, should get approved, albeit without as strong a label. Both have won breakthrough therapy designations.
Combination hopes, of course...
Given that they act on kidney tumours differently it was not surprising to see the issue of combination therapy come up, a topic happily echoed by Exelixis's chief executive, Mike Morrissey, after the researchers’ unveiling of data to the media.
“There was a lot of interest in doing that before the topline data came out, but you would imagine that afterward we’ve been inundated with people saying, ‘I’ll do that,’” Mr Morrissey said.
Exelixis and Bristol-Myers are supporting a National Institutes of Health phase I dose-ranging trial testing a combination of Opdivo and Cometriq and a three-part combo with Yervoy.
...and also monotherapy
Regardless of combination hopes, Mr Morrissey believes that the progression-free survival benefit shown for Cometriq – 7.4 months vs 3.8 months for Afinitor – will be persuasive as a monotherapy.
“The feedback from community doctors is that progression-free survival is an important parameter that they use because it’s immediate feedback; if a tumour shrinks, you can tell that to a patient,” he said.
On the other hand, overall survival is the gold standard, and one that had the lead investigator of its study, Dr Padmanee Sharma, an immuno-oncology and genitourinary specialist at MD Anderson Cancer Centre, declaring that she would reach first for the Opdivo without question.
Regulators will be happy to have an agent that can show this benefit – and it is probable that Opdivo will be first to market with this claim.