ASCO GU: With 2-year data, the jury's still out on the kidney cancer race between Opdivo-Cabometyx and Keytruda-Inlyta

When Bristol Myers Squibb and Exelixis first unveiled kidney cancer data for the combination of Opdivo and Cabometyx last fall, industry watchers couldn’t determine a clear winner between that duo and Merck & Co. and Pfizer’s Keytruda-Inlyta cocktail. Now, with longer-term data, the jury’s still out.

In previously untreated kidney cancer, the Opdivo-Cabometyx combo slashed the risk of death by 34% compared with Pfizer’s older drug Sutent. The data, from a 23.5-month follow-up of the phase 3 CheckMate-9ER trial, was released for the virtual American Society of Clinical Oncology 2021 Genitourinary Cancers Symposium.

Sutent patients lived a median 29.5 months after therapy, while the median overall survival for the Opdivo-Cabometyx combo was not reached, Jonathan Cheng, M.D., BMS’ head of oncology development, said in an interview.

The life-extension data again looked very similar to what Keytruda and Inlyta previously posted in the Keynote-426 trial. In that phase 3, after a minimum of 23 months of follow-up, the risk reduction was 32%, which may seem slightly below that of the Opdivo regimen.

Notice the difference between the “median” and the “minimum” between the two data cutoffs, though. In fact, according to results published in The Lancet Oncology, the Keytruda-Inlyta combo’s 32% death risk reduction still held true after a median follow-up of 30.6 months.

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Overall survival benefits appear to shrink for immuno-oncology regimens in front-line kidney cancer as follow-up continues. Previously, at the 18-month follow-up mark, the risk reduction amounted to 40% for the Opdivo-Cabometyx therapy; the rate was 41% for Keytruda-Inlyta after 17 months.

On some of the other efficacy markers—such as risk reduction on tumor progression, the rate of tumor response and duration of response—the two regimens both have wins against each other.

While it’s still hard to make a solid judgment between the two regimens, Cheng pointed to Cabometyx’s long experience in kidney cancer since its first FDA approval in 2016.

“Cabo is specifically well-known to the kidney cancer oncologic community ... because it has single-agent approval, and the safety profile is well-understood, including the discontinuation rate,” he said.

But as one analyst sees it, the first-line kidney cancer I-O/TKI winner may be a different regimen entirely. That title may belong to Merck and Eisai’s Keytruda-Lenvima pairing, SVB Leerink analyst Daina Graybosch said in a Tuesday note to clients.

RELATED: Merck, Eisai further complicate kidney cancer race with Keytruda-Lenvima win

At ASCO GU, Merck and Eisai will show that Keytruda and Lenvima cut the risk of death—also by 34%—after 24 months of follow-up in the Keynote-581 trial. But Graybosch pointed to several bright spots in the dataset in favor of the new contender.

Specifically, the Keytruda-Lenvima duo cut the risk of disease progression or death by a whopping 61% over Sutent, higher than the 48% and 29% for Opdivo-Cabo and Keytruda-Inlyta, respectively. The trial also found a better tumor response rate, longer duration of response, and more complete responses in Keytruda-Lenvima patients.

Industry opinion leaders believe complete response rate predicts long-tail survival, Graybosch said. Cross-trial comparisons should be made with caution, given differences in study design and baseline patient profile.

Graybosch said she will keep a close eye on some important details on treatment discontinuation rate, where, as Cheng hinted, Opdivo-Cabo looks to have the best profile.