When Bristol Myers Squibb this weekend unveiled a new trial win for an Opdivo combo in kidney cancer, industry watchers’ knee-jerk reaction was to compare the results with those from Merck & Co.’s rival PD-1 drug Keytruda. But as one analyst sees it, it may be marketing prowess—not purely data—that determines a victor in the market.
The closely watched CheckMate-9ER trial in previously untreated renal cell carcinoma was a clear success for the combination of Opdivo and Exelixis’ TKI Cabometyx. The pairing cut the risk of death by 40% compared with Pfizer’s older drug Sutent, according to data presented at the European Society of Medical Oncology virtual annual meeting.
That headline overall survival showing was numerically very similar to that from a pairing of Keytruda and Pfizer’s next-gen TKI, Inlyta, in the Keynote-426 trial. But for prescribing oncologists, comparing data between the trials is “incredibly time-consuming and confusing,” SVB Leerink analyst Daina Graybosch wrote in an investor’s note on Sunday.
For that reason, “we believe commercial execution will be particularly important—something Merck has consistently performed at the top level,” she wrote.
Arriving at that conclusion took some serious digging. First, the data unveiled at ESMO came from a median follow-up of 18 months. As Graybosch noted, treatment outcomes “evolve considerably” with more follow-up time for immuno-oncology regimens in kidney cancer.
For example, in Keynote-426, the reduction in death risk fell from 41% at 17 months of follow-up to 32% at 23 months of follow-up. Graybosch said she was surprised to see the lock date on CheckMate-9ER’s database, as just five more months of follow-up would give oncologists a more direct comparison with Keynote-426.
“Conspiracy theorists may speculate that Bristol Myers Squibb and Exelixis carefully chose the cut of data presented to give their combination the best first impression and that, as we get more data, their combination may look weaker,” she said.
Of course, cross-trial comparisons have their inherent problems such as differences in patient characteristics. Comparing outcomes in each patient risk subgroup would represent an apples-to-apples comparison, but the investigator presenting CheckMate-9ER dodged questions about different risk groups during the presentation’s Q&A sessions, Graybosch noted.
The SVB Leerink analyst figures that duration of response is the best efficacy marker for comparing the drugs’ benefit. There, Bristol’s fully owned dual immunotherapy cocktail of Opdivo and Yervoy chalked up a win; the median hadn't been reached at the last look-in on the CheckMate-214 trial, which also used Sutent as a comparator. As for the TKI combos, the durations of response were very similar, at 20.2 months for Opdivo-Cabometyx after 18 months of follow-up and at 20.9 months for Keytruda-Inlyta after 17 months of follow-up.
Overall, Graybosch and her colleagues expect doctors to continue to prefer the Opdivo-Yervoy pairing, “especially for patients with slower growing, smaller tumors,” she said. As for patients with aggressive disease, oncologists will choose their favorite TKI combo, she predicted.
Right now, Merck has the first-mover advantage, but Bristol and Exelixis can rely on existing use of both Opdivo and Cabometyx—which are separately approved in kidney cancer—to get oncologists to try their combo out, Graybosch said. The only thing is, it’s not clear how hard BMS will promote the Cabometyx option when it already has the wholly-owned Yervoy pairing.