Perioperative Pembrolizumab Improves Survival Vs Chemo in Resectable NSCLC

In an earlier analysis of the KEYNOTE-671 trial (NCT03425643), an independent data monitoring committee highlighted that the pembrolizumab-based regimen led to a statistically significant and clinically meaningful improvement in EFS compared with placebo.

Pembrolizumab (Keytruda) plus chemotherapy followed by surgical resection and adjuvant pembrolizumab produced a clinically meaningful and statistically significant improvement in overall survival (OS) compared with placebo in patients with resectable non–small cell lung cancer (NSCLC), according to a press release on findings from a pre-specified interim analysis of the phase 3 KEYNOTE-671 trial (NCT03425643).¹

Investigators reported that the pembrolizumab-based regimen’s OS benefit fulfilled one of the study’s dual primary end points. Additionally, the safety profile of the experimental treatment was comparable with prior reports of pembrolizumab.

Investigators plan to disclose complete results from the KEYNOTE-671 trial at the 2023 European Society for Medical Oncology (ESMO) Congress. Investigators also plan to discuss their findings with international regulatory health authorities.

“This is a significant milestone in the treatment of resectable [NSCLC], as it represents the first phase 3 study to show a statistically significant [OS] benefit for these patients with stage II, IIIA, or IIIB [NSCLC],” Marjorie Green, MD, senior vice president and head of late-stage oncology, global clinical development at Merck Research Laboratories, said in the press release.1 “These results build upon the previously reported event-free survival [EFS] data, and demonstrate the potential for this [pembrolizumab]-based regimen to help extend the lives of these patients. We're excited by the progress we have made to help patients with earlier stages of [NSCLC], who are in need of additional treatment options.”

In the double-blind phase 3 KEYNOTE-671 trial, investigators randomly assigned 786 patients to one of 2 treatment arms. Patients received 200 mg of pembrolizumab intravenously or matched placebo every 3 weeks for up to 4 cycles plus 75 mg/m² of cisplatin intravenously on day 1 of each cycle and 1000 mg/m² of gemcitabine intravenously on days 1 and 8 or 500 mg/m² of pemetrexed intravenously. Additionally, patients received surgery followed by adjuvant pembrolizumab or placebo for up to 13 cycles.

The trial’s other dual primary end point was EFS per RECIST v1.1 criteria. Secondary end points included major pathologic complete response (pCR), quality of life, perioperative complications, and treatment discontinuation due to adverse effects.

Patients 18 years and older with previously untreated and pathologically confirmed resectable stage II, IIIA, or IIIB NSCLC and adequate organ function were able to enroll on the trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1 and available formalin-fixed paraffin embedded tumor tissue sample blocks.

In an earlier analysis of the KEYNOTE-671 trial, an independent data monitoring committee highlighted that the pembrolizumab-based regimen led to a statistically significant and clinically meaningful improvement in EFS compared with placebo.² Additionally, the experimental treatment significantly improved the secondary end points of pCR and major pathological response at the time of the analysis.

“By moving this [pembrolizumab]-based regimen into earlier stages of [NSCLC], we may be able to significantly reduce the risk of recurrence for these patients,” Eliav Barr, MD, senior vice president and head of global clinical development at Merck Research Laboratories, said in a press release at the time the EFS data were released.²

References

1. Merck announces pivotal KEYNOTE-671 trial meets dual primary endpoint of overall survival (OS) in resectable stage II, IIIA or IIIB non-small cell lung cancer (NSCLC). News release. Merck. October 10, 2023. Accessed October 10, 2023. https://shorturl.at/BE289
2. Merck announces phase 3 KEYNOTE-671 trial met primary endpoint of event-free survival (EFS) in patients with resectable stage II, IIA, or IIIB non-small cell lung cancer. News release. Merck. March 1, 2023. Accessed October 10, 2023. bit.ly/3J0vtim