ESMO: Pfizer's Lorbrena blows Xalkori out of the water in bid for front-line, ALK-positive lung cancer use

Pfizer’s Lorbrena didn’t just top predecessor Xalkori in a recent head-to-head trial in previously untreated, ALK-positive non-small cell lung cancer. Lorbrena obliterated it.

The third-generation ALK inhibitor posted a 72% reduction in the risk of disease progression or death compared with the elder med—not an easy feat, considering Xalkori was a “very active comparator,” said Andy Schmeltz, global president and general manager of Pfizer’s oncology unit.

RELATED: Pfizer's Lorbrena makes play for earlier lung cancer use with Xalkori-topping data

And that’s not all. Lorbrena also held off brain metastases—which are a “big issue” in ALK-positive disease, presenting in up to 40% of patients—to hit a key secondary endpoint of the phase 3 Crown study, presented over the weekend at the European Society for Medical Oncology’s virtual congress.

At the 12-month mark, more than 96% of Lorbrena patients had seen no CNS progression, compared with 60% of those in the study’s Xalkori arm.

Schmeltz didn’t mince words, calling the data “stunning” and “practice-changing.”

“We’re very proud of it, and we look forward to enabling patients to benefit,” he said.

The company is hoping that happens sooner rather than later; it’s working to get its submissions in to regulators around the world as quickly as possible. In the U.S., its application will be considered under the FDA’s Real-Time Oncology Review program.

RELATED: Pfizer snags OK for Xalkori follow-up Lorbrena in its 3rd cancer approval in 2 months

Of course, Xalkori isn’t the only ALK inhibitor cleared for newly diagnosed patients. If Lorbrena can snag an approval, it’ll have to face off against Roche’s Alecensa, which beat out Xalkori in a head-to-head study on its way to a first-line approval in 2017; Takeda's Alunbrig, which accomplished the same feat before nabbing an FDA green light this past May; and Novartis’ Zykadia, which also hit the first-line market in 2017.

But the way Pfizer sees it, the latest results put Lorbrena in pretty good shape. “The Crown results, we believe, will position Lorbrena to be highly competitive with the second-generation ALK inhibitors in the first-line setting,” Schmeltz said, adding that the data “really sets the stage.”

Lorbrena has already done well for itself in second-line patients since first hitting the scene in late 2018. In the U.S., it already holds about 65% of the market, Schmeltz said—a figure that’s only likely to grow after the drug’s Crown performance.

It’s currently used after Alecensa, and “we would imagine for patients” who have already been on the Roche drug, “this will just truly reinforce Lorbrena as the standard of care,” Schmeltz said—not to mention providing “a compelling benefit-risk proposition for new patients.”

Editor's note: This story previously stated that both Alecensa and Zykadia had topped Xalkori in trials; only Alecensa has.