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Merck steps up to challenge Roche with big Keytruda breast cancer win

Right now, Roche’s Tecentriq is the only drug in its class with an approval in previously untreated, metastatic triple-negative breast cancer, a particularly aggressive form of the disease. But Merck is laying out its case to change that.

Its checkpoint inhibitor Keytruda, given alongside chemo, cut down the risk of disease progression or death by 35% against solo chemo in patients with high levels of the biomarker PD-L1—those with a combined positive score of 10 or greater, to be exact.

Patients went a median 9.7 months on the Keytruda-chemo combo without their disease worsening, compared with 5.6 months for those in the chemo-only group, Merck said ahead of the American Society of Clinical Oncology (ASCO) virtual annual meeting. 

The trial, Keynote-355, will continue, to see whether Keytruda can hit the other primary endpoint by extending patients’ lives.

Meanwhile, Merck will use the data to shoot for a new indication for Keytruda, setting the drug up to battle Tecentriq in the marketplace. Roche’s contender grabbed its FDA green light last March on the back of data showing it could pare down the risk of disease worsening or death by 20% in tandem with chemo drug Abraxane.

While comparing data from separate trials is always risky—the only surefire way to measure the performance of two drugs against each another is with a head-to-head trial—it happens anyway, especially among analysts and investors, who will undoubtedly pit Merck’s new results against Roche’s.

While the chemo arm performed comparably in the two trials—staving off progression by 5.6 months in Merck’s trial and 5.5 months in Roche’s—the 9.7-month benefit for the Keytruda-chemo combo is longer than the 7.2-month figure the Tecentriq-Abraxane pairing turned up.

“Cross-trial comparisons are difficult and have a lot of limitations,” said Roy Baynes, M.D., Merck SVP and head of global clinical development. “Having said that, we do think that -355 compares very favorably.”

Keytruda also has another tally in the TNBC win column thanks to the Keynote-522 trial. That study showed last September that among pre-surgery patients, the drug, paired with chemo, could beat solo chemo at clearing all signs of cancer from breast and lymph node tissue by the time of surgery, doing so in 64.8% of patients.

“I think we are the only (immuno-oncology) drug that has shown the results that we have shown in the neoadjuvant setting, so I think the practicing oncologists will have to review the data and evaluate the risk-benefit basis based upon what they see,” Baynes said.

Another potential leg up for Merck? The New Jersey drugmaker’s study allowed physicians to use a wider range of chemo options than Roche’s did, meaning an approval might “allow docs more flexibility, which could be a commercial advantage,” Evercore ISI analyst Umer Raffat wrote in a February note to clients.

“We sought in this trial to be inclusive rather than specific” to reflect “how the disease is treated,” Baynes said, adding that “we believe the data show robust efficacy across all the available chemotherapies that are used commonly.”

But Roche is sitting on a pretty hefty market lead, as Leerink Partners’ Daina Graybosch wrote in her own February research note. “We think Merck may struggle to gain a foothold for Keytruda in metastatic triple-negative breast cancer,” she said, pointing out that “by the time Merck enters the market, Roche will have a two-year lead, in addition to a more predictive biomarker for clinical benefit (immune-cell (IC) PD-L1).”