Merck’s Keytruda wins coveted FDA nod around surgery for early lung cancer—with a surprise

Up until this point, immune checkpoint inhibitors have been allowed to treat early-stage non-small cell lung cancer (NSCLC) either before or after surgery. Thanks to a new FDA approval, a continuous immunotherapy regimen for use on both sides of surgery is now available for certain patients.

The approval, for Merck’s Keytruda, clears the PD-1 inhibitor to be used both as part of a neoadjuvant regimen before surgery and as an adjuvant therapy after surgery in patients with resectable NSCLC. Patients also take chemotherapy during presurgical treatment.

In a coveted win for Merck, Keytruda’s updated label (PDF) already includes data showing that, compared with neoadjuvant chemo alone, the addition of perioperative Keytruda significantly cut the risk of death by 28% in the Keynote-671 study.

Patients who took neoadjuvant chemo alone lived a median 52.4 months, while the median result for the Keytruda arm wasn’t reached by the time of the analysis, according to Monday’s FDA label update.

The inclusion of the overall survival data comes as a surprise given that it was only last week when Merck said the Keynote-671 trial met its overall survival goal. The detailed data were originally expected to be shared for the first time at the upcoming European Society for Medical Oncology 2023 Congress in the next few days. 

The approval could meaningfully increase Keytruda’s sales outlook, even though the Merck drug is already one of the best-selling therapies in the world. But competition could be looming as Bristol Myers Squibb and AstraZeneca have reported positive readouts in the same perioperative setting.

Besides the overall survival benefit, Keynote-671 showed that, when added to neoadjuvant chemo alone, pre- and post-surgical use of Keytruda slashed the risk of tumor recurrence, progression or death by 42% in patients with resectable stage 2 to 3b NSCLC.

Leerink Partners analyst Daina Graybosch, Ph.D., previously called Keytruda’s event-free survival result “impressive.” Still, the efficacy figure narrowly missed the 45% bar that doctors told Leerink could convince them patients are seeing extra benefit from continued adjuvant use of a PD-1 inhibitor on top of neoadjuvant treatment.

Before this approval for Keytruda, BMS' Opdivo last year won a go-ahead as a neoadjuvant therapy to treat stage 1b to 3a NSCLC. In the CheckMate-816 trial, adding Opdivo to chemo before surgery improved event-free survival (EFS) by 37% in that patient group.

In addition, just last month, BMS said Opdivo significantly improved EFS when used both before and after surgery in the CheckMate-77T trial. Detailed data from CheckMate-77T will be presented at ESMO.

Previously, a longer-term follow-up of CheckMate-816—released in March—showed that neoadjuvant Opdivo reduced the risk of death by 38%. The result had yet to reach statistical significance.

The extent of Opdivo’s EFS improvement and Keytruda’s overall survival benefit will help doctors decide which therapy to use, and whether continued PD-1 treatment in the adjuvant setting is necessary after neoadjuvant therapy.

Besides Merck and BMS, AstraZeneca has also reported positive EFS data for perioperative Imfinzi from the phase 3 AEGEAN trial. The analysis likely won’t lead to any regulatory action for now given its short follow-up time.

Meanwhile, the readout from Roche’s IMpower-030 trial for perioperative Tecentriq has been repeatedly delayed and is now expected in 2024.

As for Keytruda, the drug also boasts a perioperative approval to treat certain patients with triple negative breast cancer.