Results from the phase 3 PEARLS/KEYNOTE-091 trial showed improved disease-free survival with pembrolizumab vs placebo for patients with completely resected early-stage non–small cell lung cancer, without regard surgical treatment, extent of disease, or adjuvant chemotherapy.
Improved disease-free survival (DFS) was observed when pembrolizumab (Keytruda) vs placebo was administered to patients with completely resected early-stage non–small cell lung cancer (NSCLC), regardless of the type of surgical resection, degree of lymph node involvement, tumor size, and type and extent of adjuvant chemotherapy, according to results from an exploratory analysis of the phase 3 PEARLS/KEYNOTE-091 trial (NCT02504372) presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
The median DFS in the overall population was 53.6 months (95% CI, 39.2-not reached [NR]) in the pembrolizumab arm vs 42.0 months (95% CI, 31.3-NR) in the placebo arm (HR, 0.76; 95% CI, 0.63-0.91; P = .0014). Median DFS for those with a PD-L1 tumor proportion score (TPS) of 50% or more was NR in the pembrolizumab group (95% CI, 44.3-NR) or the placebo group (95% CI, 35.8-NR; HR, 0.82; 95% CI, 0.57-1.18; P = .014). Median overall survival in the entire cohort was NR in either arm, but favored the pembrolizumab arm slightly (HR, 0.87; 95% CI, 0.67-1.15; P = .17).
Patients with stage IB to IIIA NSCLC following complete tumor resection were randomized 1:1 to either the pembrolizumab (n = 590) or placebo arm (n = 587). Patients were further stratified by PD-L1 expression, with 168 patients in the pembrolizumab arm and 165 in the placebo arm having a TPS of 50% or more. Patients received either pembrolizumab at 200 mg every 3 weeks for up to 18 cycles or matched placebo.
Eligibility for treatment included having confirmed stage IB NSCLC with tumor size of at least 4 cm or stage II to IIIA disease, a complete surgical resection with negative margins, and tumor tissue for PD-L1 testing. Eligibility for randomization included having no evidence of disease, an ECOG performance score of 0 or 1, and prior adjuvant chemotherapy.
In the overall cohort, the median age was 65 years for both the pembrolizumab and placebo arms, two-thirds of patients were men, and a majority were treated in Western Europe. An ECOG performance score of 1 was reported in 35.6% vs 41.6%, respectively, with 85.3% vs 88.8% being current or former smokers, and 67.5% vs 61.8% having nonsquamous histology. Adjuvant chemotherapy was given in 85.8% of patients in the pembrolizumab group and 85.9% of the placebo group. Patients mostly presented with stage II disease, at 55.8% vs 57.6%. Additionally, EGFR mutations were observed in 6.6% vs 5.8% of patients in the pembrolizumab and placebo groups, respectively, with ALK translocation occurring in 1.2% each.
In those with a PD-L1 TPS of 50% or more, the median age was 64.5 years in the pembrolizumab arm and 65.0 years in the placebo arm. Most patients were men (72.0% vs 70.3%) and a majority were treated in Western Europe (53.6% vs 53.9%). An ECOG performance score of 1 was observed in 31.0% vs 38.8%, with 91.7% vs 92.1% being current or former smokers, and 61.3% vs 63.6% having nonsquamous histology. Adjuvant chemotherapy was given in 85.1% vs 85.5% of patients. Patients in this group were most likely to present with stage II disease at 56.5% vs 56.4%. Additionally, EGFR mutations were observed in 3.6% vs 3.0% of patients in the pembrolizumab and placebo groups, respectively, with ALK translocation occurring in 1.8% and 0%.
Between the pembrolizumab and the placebo arms, patients were most likely to undergo a lobectomy (78.1% vs 79.0%), have a tumors status of 0 (39.5% vs 43.8%) or 1 (39.5% vs 38.0%), and present with a tumor 4 cm or greater in size (57.1% vs 59.3%). A total of 84 patients (14.2%) in the pembrolizumab arm and 83 (14.1%) in the placebo arm did not receive adjuvant chemotherapy due to patient refusal of treatment in 36 vs 30 patients, physician decision in 46 vs 47, and unknown reasons for 2 vs 6, respectively.
Of those who did receive adjuvant chemotherapy, a majority in both the pembrolizumab and placebo groups had 3 to 4 cycles (79.8% vs 80.4%, respectively). Patients received either carboplatin-based therapy (31.2% vs 29.1%), cisplatin-based therapy (51.0% vs 52.3%), or carboplatin- and cisplatin-based therapy (3.6% vs 4.4%). The specific regimens received between the 2 groups were carboplatin plus paclitaxel in 10.2% of patients receiving pembrolizumab and 12.8% on placebo; carboplatin plus vinorelbine for 13.7% and 11.9%, respectively; cisplatin plus gemcitabine for 4.6% and 5.1%; cisplatin plus vinorelbine for 40.8% and 42.6%; and other regimens for 16.4% and 13.5%.
DFS outcomes by baseline factors consistently favored the pembrolizumab arm, including receipt of bilobectomy (HR, 0.85; 95% CI, 0.43-1.69), lobectomy (HR, 0.78; 95% CI, 0.64-0.96), and pneumonectomy (HR, 0.71; 95% CI, 0.40-1.24); lymph node status involvement of pN0 (HR, 0.63; 95% CI, 0.46-0.86) or pN1 (HR, 0.77; 95% CI, 0.57-1.03); and tumor size of 4 cm or less (HR, 0.91; 95% CI, 0.69-1.20) or greater than 4 cm (HR, 0.70; 95% CI, 0.55-0.89).
DFS outcomes stratified by use, extent, and type adjuvant chemotherapy favored the pembrolizumab arm, including use of 1 to 2 cycles (HR, 0.59; 95% CI, 0.28-1.26) or 3 to 4 cycles (HR, 0.74; 95% CI, 0.61-0.91) and combinations of carboplatin plus vinorelbine (HR, 0.51; 95% CI, 0.31-0.83), cisplatin plus gemcitabine (HR, 0.65; 95% CI, 0.30-1.40), cisplatin plus vinorelbine (HR, 0.74; 95% CI, 0.55-0.98), and other combinations (HR, 0.69; 95% CI, 0.41-1.14). For the placebo arm, DFS outcomes favored those who did not received adjuvant chemotherapy (HR, 1.25; 95% CI, 0.76-2.05) and the use of carboplatin plus paclitaxel (HR, 1.21; 95% CI, 0.73-1.98).
O’Brien M, Paz-Ares L, Jha N, et al. EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 study of pembrolizumab versus placebo for completely resected early-stage non-small cell lung cancer (NSCLC): Outcomes in subgroups related to surgery, disease burden, and adjuvant chemotherapy use. J Clin Oncol. 2022;40(suppl 16):8512. doi: 10.1200/JCO.2022.40.16_suppl.8512