#KEYNOTE 042 TRIAL#
#KEYNOTE 042 PLUS#

The objective of our study was to evaluate the efficacy and safety of pembrolizumab vs platinum-based chemotherapy in Chinese patients with PD-L1-positive, locally advanced/metastatic NSCLC without targetable EGFR/ALK alterations. The current report provides results from the KEYNOTE-042 China study, which includes patients enrolled from China in the global or China extension study of KEYNOTE-042 (data cutoff, February 21, 2020). As previously reported, the anti-PD-1 antibody pembrolizumab significantly prolonged OS compared with platinum-based chemotherapy in patients with previously untreated metastatic NSCLC without sensitizing EGFR/ALK alterations and PD-L1 tumor proportion score (TPS) ≥50% in the KEYNOTE-024 study, 7, 8 and in patients with TPS ≥1% in the global KEYNOTE-042 study (data cutoff, FebruN = 1274).

#KEYNOTE 042 TRIAL#

Here, we present results from a Phase 3 clinical trial evaluating first-line anti-PD-1 therapy in Chinese patients with advanced PD-L1-positive NSCLC. In this prior study, the PD-1 inhibitor nivolumab improved overall survival (OS) compared with docetaxel. At present, CheckMate-078 is the only Phase 3 study that has evaluated anti-PD-1 therapy in a predominantly Chinese patient population with previously treated NSCLC. 1, 2 Because Asian patients are often underrepresented in international randomized clinical trials of anti-PD-(L)1 therapies, 3 and disease characteristics (eg, EGFR mutation prevalence) 4 and responses to anticancer therapy may differ between Asian and Caucasian populations, 5 there is a need to evaluate these treatments specifically in Asian patients. Monoclonal antibodies targeting programmed death 1 and programmed death ligand 1 (PD-1) have demonstrated significant improvements in clinical outcomes relative to standard chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC). Consistent with the global KEYNOTE-042 study, pembrolizumab improved OS vs chemotherapy in this study of Chinese patients with locally advanced/metastatic NSCLC and PD-L1 TPS ≥1%, supporting first-line pembrolizumab monotherapy for PD-L1-positive advanced/metastatic NSCLC in China. In 22 patients who completed 35 cycles of pembrolizumab, objective response rate was 77.3% and median duration of response was 27.6 months.

Grade 3 to 5 treatment-related adverse events occurred less frequently with pembrolizumab vs chemotherapy (19.5% vs 68.8%). At data cutoff (Februmedian follow-up, 33.0 months), pembrolizumab was shown to improve OS vs chemotherapy in patients with PD-L1 TPS ≥50% (hazard ratio, 0.63 ), TPS ≥20% (0.66 ) and TPS ≥1% (0.67 ). Two hundred sixty-two patients (pembrolizumab, n = 128 chemotherapy, n = 134) were enrolled from China.

Primary endpoints were OS in patients with PD-L1 TPS ≥50%, ≥20% or ≥1%.

#KEYNOTE 042 PLUS#

Patients were randomized 1:1 (stratified by ECOG performance status 0 vs 1, squamous vs nonsquamous histology and PD-L1 tumor proportion score ≥50% vs 1%-49%) to 35 cycles of pembrolizumab 200 mg every 3 weeks (Q3W) or investigator's choice of 4 to 6 cycles of carboplatin plus paclitaxel or pemetrexed Q3W with optional pemetrexed maintenance for nonsquamous tumors. We present results from patients in KEYNOTE-042 enrolled from China in the global or extension study (NCT03850444 protocol identical to global study).

In the global KEYNOTE-042 study (, NCT02220894), pembrolizumab significantly improved overall survival (OS) vs chemotherapy in patients with previously untreated programmed death ligand 1 (PD-L1)-positive locally advanced/metastatic non–small-cell lung cancer (NSCLC) without EGFR/ ALK alterations.

Keynote 042