Pembrolizumab improves survival in untreated metastatic nonsquamous NSCLC
Patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC) may have their overall survival (OS) and progression-free survival (PFS) approximately doubled with pembrolizumab in combination with platinum-based chemotherapy vs chemotherapy alone, according to updated results of the KEYNOTE-189 trial reported at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.
After a median study follow-up of 23.1 months and a median survival follow-up of 18.7 months, median OS was 22 months in patients receiving pembrolizumab/chemotherapy (n=410) compared with 10.7 months in those receiving placebo/chemotherapy (n=206) (hazard ratio [HR], 0.56; 95 percent confidence interval [CI], 0.45 to 0.70). [Gadgeel S, et al, ASCO 2019, abstract 9013]
OS rates at 12 months and 24 months were 70 percent vs 48.1 percent and 45.5 percent vs 29.9 percent, respectively, for patients in the pembrolizumab/chemotherapy vs placebo/chemotherapy group.
PFS was also approximately doubled in patients receiving pembrolizumab/chemotherapy vs placebo/chemotherapy, with a median of 9 months vs 4.9 months (HR, 0.48; 95 percent CI, 0.40 to 0.58). PFS rates at 12 months and 24 months were 38.8 percent vs 16.8 percent and 20.5 percent vs 1.5 percent, respectively.
PFS in the second-line setting (PFS2), defined as time from randomization to objective tumour progression on next-line treatment or all-cause mortality, was likewise approximately doubled in the pembrolizumab/chemotherapy vs placebo/chemotherapy group (median, 17 months vs 9 months; HR, 0.49; 95 percent CI, 0.40 to 0.59).
Benefits in OS, PFS and PFS2 were observed with pembrolizumab regardless of patients’ PD-L1 tumour proportion score (TPS). HRs for OS were 0.59 (95 percent CI, 0.39 to 0.88), 0.62 (95 percent CI, 0.42 to 0.92), and 0.52 (95 percent CI, 0.36 to 0.74) in those with PD-L1 TPS ≥50 percent (n=202), 1–49 percent (n=186), and <1 percent (n=190), respectively. Corresponding HRs for PFS were 0.36 (95 percent CI, 0.26 to 0.51), 0.51 (95 percent CI, 0.36 to 0.73), and 0.64 (95 percent CI, 0.47 to 0.89), respectively, while HRs for PFS2 were 0.47 (95 percent CI, 0.33 to 0.69), 0.59 (95 percent CI, 0.41 to 0.86), and 0.46 (95 percent CI, 0.33 to 0.66), respectively.
“The benefit of pembrolizumab plus chemotherapy was observed despite the fact that 53.9 percent of patients in the placebo/chemotherapy group received a subsequent PD-1 or PD-L1 inhibitor, including 40.8 percent who crossed over in the study to receive pembrolizumab monotherapy,” the investigator noted.
According to the investigators, the safety and tolerability of pembrolizumab/chemotherapy was manageable. All-cause grade 3–5 adverse events (AEs) were reported in 71.9 percent of patients in the pembrolizumab/chemotherapy group vs 66.8 percent of those in the placebo/chemotherapy group. The rate of grade 3–5 immune-mediated AEs and infusion reactions was 10.9 percent vs 4.5 percent.
“Our data confirm that pembrolizumab should be given as part of first-line therapy to maximize outcomes in both PD-L1–expressing and PD-L1–nonexpressing, metastatic nonsquamous NSCLC,” the investigators concluded.