Merck's Keytruda hits overall survival goal in early lung cancer as FDA decision nears

What doctors described as a “messy” treatment landscape in early-stage non-small cell lung cancer (NSCLC) could get clearer thanks to a first-in-class overall survival win from Merck & Co.’s Keytruda.

Using Keytruda both before and after surgery significantly extended the lives of patients with stage 2 to 3b NSCLC in a phase 3 trial, Merck said Tuesday. The Keytruda regimen was pitted against presurgical chemo alone, while Keytruda recipients also received chemotherapy before surgery.

The Keynote-671 trial marks the first time an immunotherapy has shown a statistically significant overall survival benefit for certain patients with early-stage NSCLC, Marjorie Green, M.D., head of late-stage oncology development at Merck Research Laboratories, said in a statement.

The positive readout comes right before the FDA is expected to decide—by Monday—on Keytruda’s perioperative use as a continuous neoadjuvant-plus-adjuvant therapy in early-stage NSCLC. The trial previously met its other dual primary endpoint, showing Keytruda could reduce the risk of tumor recurrence, progression or death on the event-free survival (EFS) marker.

The updated Keynote-671 data will be presented at the European Society for Medical Oncology 2023 congress later this month. At the ESMO meeting, investigators will also share results from the CheckMate-77T trial for Bristol Myers Squibb’s Opdivo in a very similar stage 2 to 3b NSCLC perioperative setting. BMS said a few days ago that the trial hit its EFS goal.

The two datasets could offer much-needed clarity for doctors who have lately struggled to choose the appropriate treatment for early-stage NSCLC around surgery. Keytruda and Opdivo, plus Roche’s Tecentriq and AstraZeneca’s Imfinzi, have all posted positive outcomes in this setting.

One key question that has troubled doctors is whether a PD-1/L1 inhibitor is needed both before and after surgery.

Last March, Opdivo snagged FDA approval as a neoadjuvant therapy for use only before surgery. The approval was based on data from the CheckMate-816 trial, which showed that Opdivo’s addition to chemo could improve event-free survival by 37% in stage 1b to 3a NSCLC.

An updated analysis released in March showed a 38% reduction in the risk of death for the Opdivo regimen, although the number had yet to reach statistical significance.

When Merck shared Keynote-671’s 42% EFS improvement figure at the American Society of Clinical Oncology annual meeting in June, analysts and the trial investigator predicted that the study would likely hit its overall survival goal because the survival rates had already started to separate between Keytruda and the control arm at two years.

Meanwhile, AZ has previously reported that perioperative Imfinzi can reduce the EFS risk by 32% in stage 2 to 3b NSCLC, with that number coming from an interim analysis of the AEGEAN trial. The overall survival analysis for that study was immature.

Keytruda and Roche’s Tecentriq are also both approved as adjuvant therapy used only after surgery.

An overall survival benefit is one of the key considerations in deciding how to use immunotherapy around surgery, Mark Awad, M.D., Ph.D., of the Dana-Farber Cancer Institute, pointed out during a discussion at ASCO in June.