ASCO: Merck touts Keytruda's 'convergent' benefits across postsurgery lung cancer patient groups

As biopharma industry watchers wait to see whether Keytruda will hit its goal as a postsurgery treatment in early lung cancer patients with high tumor expressions of the PD-L1 biomarker, Merck & Co. is rolling out new data to show the drug’s benefits across other patient groups.

New subgroup analyses of the phase 3 KEYNOTE-091 trial offered “convergent validity” that patients can benefit from Keytruda as an adjuvant treatment for their early non-small cell lung cancer (NSCLC) after surgery, Greg Lubiniecki, M.D., vice president of clinical research at Merck Research Laboratories, said in an interview with Fierce Pharma.

Merck has previously shown that providing Keytruda as part of an adjuvant regimen—that may include chemotherapy—can reduce the risk of tumor returning or patient death after surgical removal of stage 1B to 3A NSCLC by 24%. Now, the New Jersey pharma is laying out details for various patient subgroups. In these groups, Keytruda seems to work better for some patients than others.

Broadly speaking, Keytruda offered event-free survival advantages across the adjuvant chemotherapies used and in patients with different lymph node involvement, Lubiniecki said. The drug also helped regardless of the size of the primary tumor.

Still, in 231 patients with a high number of lymph nodes involved, classified as pN stage 2, the risks of tumor recurrence or death were the same with or without Keytruda. And for 167 patients who didn’t receive adjuvant chemotherapy, the risk somehow favored those who didn’t get the Merck drug.

The same thing happened to a group of 135 patients who got carboplatin and paclitaxel as their adjuvant chemo. Patients who had Keytruda on top of that doublet chemo appeared to perform worse than those who got the chemo alone.

Altogether, the trial randomized 1,177 patients.

Elsewhere, data favored Keytruda across three different types of surgery, by tumor size both above 4 cm and at or below 4 cm, and by the number of chemo cycles, plus several other chemo doublet regimens. Detailed analyses of those subgroups will be presented at the 2022 American Society of Clinical Oncology (ASCO) annual meeting.

Lubiniecki cautioned against reaching firm conclusions about those subgroup analyses because the effects recorded in those small groups were uncertain from a statistical point of view. Besides, the trial was not designed to run those analyses in a controlled manner, he said.

But the new analyses offer physicians evidence that may one day help guide Keytruda’s use as an adjuvant NSCLC treatment if it eventually wins an FDA go-ahead.

Experts are now waiting for more mature data from KEYNOTE-091 on Keytruda in patients with tumor PD-L1 expression at or above 50%. At an interim analysis, Keytruda only showed an 18% disease-free survival risk reduction in those PD-L1-high patients and didn’t meet the statistical significance bar.

Roy Baynes, M.D., Ph.D., former chief medical officer of Merck Research Laboratories, previously argued that the total events of disease recurrence and death was still too small in the PD-L1-high group.

Merck doesn’t have an update on the PD-L1-high population at ASCO 2022. Lubiniecki noted there will be an additional analysis of the KEYNOTE-091 trial but wouldn’t say when that will happen.