Merck & Co.’s Keytruda reigns over the immuno-oncology market for metastatic lung cancer. But in controlling earlier-stage disease, the anti-PD-1 therapy has posted some perplexing results.
When used after surgery, Keytruda topped placebo at keeping disease from returning and keeping patients alive, regardless of their PD-L1 biomarker status, Merck said Monday. The results were from a test in patients with stage IB to IIIA non-small cell lung cancer called Keynote-091 who might also have taken chemotherapy post surgery.
The “statistically significant and clinically meaningful” improvement showed up in an interim analysis of the phase 3 trial, Merck said.
The success came three months after Roche’s Tecentriq became the first checkpoint inhibitor to win an FDA nod for post-surgery NSCLC, the so-called adjuvant setting.
The broad range of patients covered in Keytruda’s data could have meant a resounding win for the Merck drug, given that Tecentriq is only allowed in PD-L1-positive, stage II to IIIA disease. But the Keytruda trial also returned one caveat.
Among a subset of patients—those whose tumors express high levels of PD-L1 at a tumor proportion score of at least 50%—Keytruda showed an improvement in disease-free survival, but it failed to pass the statistical significance bar. Therefore, the trial didn’t meet its co-primary endpoint at this point.
That lack of showing was surprising because these checkpoint inhibitors have historically worked better in PD-L1-high patients than in low expressers. Just consider Tecentriq’s approval for NSCLC treatment after surgery. The drug's label covers patients with PD-L1 expression of at least 1%, but in patients with levels between 1% and 49%, the drug pared down the the risk of disease recurrence or death by only 13% when added to chemo in stage II to IIIA NSCLC.
When Roche presented that subset of data at the European Society of Medical Oncology’s 2021 meeting, several experts argued that Tecentriq’s adjuvant use—if any—should be limited to PD-L1-high patients.
Merck has yet to disclose detailed data from the Keynote-091 trial, also known as Pearls. Researchers will continue to analyze the disease-free survival data in PD-L1-high patients and will also follow the patients to evaluate whether adjuvant Keytruda could specifically extend patients’ lives, a key secondary endpoint of the study.
Doctors have been looking to data from Keynote-091 to better understand checkpoint inhibitors’ effect in post-surgery NSCLC, given Keytruda has historically been viewed as the best in the class.
After Tecentriq’s readout, many experts had suggested they would wait for results from other PD-1/L1s or more mature overall survival data to decide whether to use these drugs in early NSCLC. But now, Keytruda is giving them more questions than answers.