Investigators of the phase 3 KEYNOTE-671 trial identify no new safety signals with pembrolizumab plus chemotherapy in those with early-stage non–small cell lung cancer.
Neoadjuvant treatment with pembrolizumab (Keytruda) plus chemotherapy followed by surgical resection and adjuvant pembrolizumab produced significant improvements in event-free survival (EFS), major pathological response, and pathological complete response (pCR) compared with neoadjuvant chemotherapy and surgery alone in patients with early-stage non–small cell lung cancer (NSCLC), according to findings from the phase 3 KEYNOTE-671 trial (NCT03425643).
The 24-month EFS estimates were 62.4% (95% CI, 56.8%-67.5%) in patients receiving pembrolizumab vs 40.6% (95% CI, 34.8%-46.3%) in those treated with chemotherapy alone. The median EFS was not reached (NR; 95% CI, 34.1 months to NR) and 17.0 months (95% CI, 14.3%-22.0%) in each respective treatment group (HR, 0.58; 95% CI, 0.46-0.72; P <.001). Investigators identified EFS benefits in the pembrolizumab arm across all patient subgroups, although they noted that these groups were small.
At 24 months, the estimated overall survival (OS) rates were 80.9% (95% CI, 76.2%-84.7%) in the pembrolizumab group compared with 77.6% (95% CI, 72.5%-81.9%) in the placebo group. Additionally, investigators reported a median OS that was NR (95% CI, NR-NR) and 45.5 months (95% CI, 42.0-NR) in each respective treatment arm (P = .02).
In the pembrolizumab and placebo groups, respectively, 30.2% (95% CI, 25.7%-35.0%) and 11.0% (95% CI, 8.1%-14.5%) of patients experienced a major pathological response. Additionally, investigators reported a pCR in 18.1% (95% CI, 14.5%-22.3%) and 4.0% (95% CI, 2.3%-6.4%) of patients in each respective group. Data from an exploratory analysis highlighted that patients who received pembrolizumab experienced an EFS benefit regardless of whether they had a major pathological response or a pCR.
“The [OS] benefit was not significant in this first interim analysis,” the study authors wrote. “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.”
Investigators of the double-blind, placebo-controlled KEYNOTE-671 trial stratified patients based on disease stage, PD-L1 tumor proportion score, histologic features, and geographic region. Patients received 200 mg of pembrolizumab or matched placebo intravenously once every 3 weeks for 4 cycles plus cisplatin or gemcitabine as part of a neoadjuvant regimen. Surgery was then performed at no more than 20 weeks following the first dose of neoadjuvant treatment, which preceded 200 mg of adjuvant pembrolizumab or placebo once every 3 weeks for up to 13 cycles.
The trial’s dual primary end points were EFS and OS. Secondary end points included major pathological response, pCR, and safety.
Patients 18 years and older with stage II, IIIA, or IIIB NSCLC considered to be resectable based on surgical consultation and investigator assessment were able to enroll on the trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1 and available tumor samples for PD-L1 assessment.
The overall study population included 797 patients, of whom 397 were assigned to the pembrolizumab group and 400 were in the placebo group. The median age in the pembrolizumab and placebo groups, respectively, was 63 years (range, 26-83) and 64 years (range, 35-81). Additionally, most patients in each respective group were male (70.3% vs 71.0%), White (63.0% vs 59.8%), and had an ECOG performance status of 0 (63.7% vs 61.5%). Most in each respective arm also had stage III disease (70.3% vs 69.8%), node stage N2 disease (42.3% vs 46.8%), nonsquamous histology (56.9% vs 56.8%), and a PD-L1 proportion score lower than 50% (66.8% vs 66.5%).
Any-grade treatment-related adverse effects (TRAEs) occurred in 96.7% of patients assigned to the pembrolizumab arm and 95.0% of those assigned to the placebo arm. The most common TRAEs in each respective arm included nausea (54.3% vs 51.1%), neutrophil count decreases (42.2% vs 41.9%), anemia (36.1% vs 33.8%) and white-cell count decreases (28.0% vs 24.6%).
TRAEs of grade 3 or higher affected 44.9% of patients receiving pembrolizumab and 37.3% of those receiving placebo. Investigators reported that the most common TRAEs of this type in each respective arm were neutrophil count decreases (20.7% vs 19.5%), anemia (7.3% vs 5.5%), white-cell count decreases (5.3% vs 5.5%), and platelet count decreases (5.1% vs 6.0%).
Wakelee H, Liberman M, Kato T, et al. Perioperative pembrolizumab for early-stage non–small cell lung cancer. N Engl J Med. 2023;389:491-503. doi:10.1056/NEJMoa2302983