medwireNews: The KEYNOTE-671 trial points to a significant improvement in event-free survival (EFS) for patients with early-stage, non-small-cell lung cancer (NSCLC) with use of pembrolizumab before and after surgery.
Heather Wakelee told delegates attending the 2023 ASCO Annual Meeting in Chicago, Illinois, USA, that results of the first prespecified interim analysis suggest that the pembrolizumab regimen “provided a statistically significant, clinically meaningful improvement in EFS.”
The phase 3 trial, which was simultaneously published in The New England Journal of Medicine, assessed the impact of adding four 3-week cycles of pembrolizumab 200 mg to standard neoadjuvant cisplatin-based chemotherapy, as well as 13 weeks of adjuvant pembrolizumab 200 mg instead of placebo.
The study population had treatment-naive resectable stage II, IIIA, or IIIB (N2) NSCLC, were aged a median 63–64 years, and 70–71% were men. Two thirds (62%) of patients were former smokers, a quarter (24–26%) were current smokers, and the remainder had never smoked. The majority of patients in the study had unknown EGFR and ALK alteration status.
After completing neoadjuvant therapy, 82.1% of the 397 patients in the pembrolizumab arm underwent planned surgery, as did 79.4% of the 400 patients given placebo. A complete resection was performed for 75.5% and 66.9%, respectively, and a corresponding 73.2% and 66.9% went onto receive at least one dose of adjuvant pembrolizumab or placebo.
The dual primary endpoint of EFS, calculated after a median of 25.2 months of follow-up, was significantly higher with pembrolizumab than placebo, at a median of unreached versus 17.0 months, and a significant hazard ratio (HR) of 0.58 that favoured the pembrolizumab arm.
The 2-year EFS rates for the pembrolizumab and control arms were 62.4% and 40.6%., respectively, and subgroup analysis “uniformly” supported the PD-1 inhibitor, with increasing benefit noted with rising PD-L1 expression, the presenter observed.
Although the second primary endpoint of overall survival (OS) did not show a significant difference at time of reporting, Heather Wakelee said that the survival curves were “starting to separate,” with median OS unreached in the pembrolizumab arm and 45.5 months in the control arm. The 2-year OS rates were 80.9% versus 77.6%, respectively.
There was also a significant perioperative pembrolizumab versus placebo benefit for rates of major pathological response (30.2 vs 11.0%,) and pathologic complete response (18.1 vs 4.0%). But the presenter said exploratory analysis indicated that the EFS was improved with pembrolizumab regardless of whether these two secondary endpoints had been achieved.
Over the full treatment period, 44.9% of pembrolizumab-treated patients experienced a grade 3 or more severe treatment-related adverse event (TRAE) compared with 37.3% of controls, with serious TRAEs reported in 17.7% and 14.3%, respectively. TRAEs led to discontinuation in 12.6% and 5.3% of patients, respectively, while fatal TRAEs occurred in 1.0% and 0.8%.
Furthermore, potentially immune-mediated AEs of grade 3 or more severe occurred in 5.8% and 1.5% of the pembrolizumab and control arms, respectively, including one case of pneumonitis in the former group.
“Neoadjuvant pembrolizumab did not affect exposure to neoadjuvant chemotherapy or the choice of surgical approach, compromise the ability to undergo surgery, or increase the incidence of surgical complications,” the study authors write.
They conclude that, when considered alongside early results from the AEGEAN and Neotorch trials, “the findings taken together support the benefit of perioperative immune checkpoint inhibition for the treatment of resectable stage II or III NSCLC.”
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2023 ASCO Annual Meeting; Chicago, Illinois, USA: 2–6 June
N Engl J Med 2023; doi:10.1056/NEJMoa2302983