Outcomes among patients (pts) with metastatic nonsquamous NSCLC with liver metastases or brain metastases treated with pembrolizumab (pembro) plus pemetrexed-platinum: Results from the KEYNOTE-189 study

Abstract

Background: KEYNOTE-189 is a randomized, placebo-controlled, Phase III study of pembro plus pemetrexed-platinum versus placebo plus pemetrexed-platinum among pts with metastatic nonsquamous NSCLC. At median follow-up of 10.5 months, pts in the pembro-combination arm had improved OS (HR, 0.49; 95% CI, 0.38-0.64; P<0.001) and PFS (HR, 0.52; 95% CI, 0.43-0.64; P<0.001) compared with pts in the placebo-combination arm. We present a retrospective, exploratory evaluation of outcomes among pts with liver and brain metastases at baseline from an updated analysis.

Methods: Pts with untreated metastatic nonsquamous NSCLC, ECOG PS 0/1, and without EGFR/ALK alteration were randomized 2:1 to receive up to 35 Q3W cycles of pembro 200 mg or placebo plus 4 cycles of pemetrexed 500 mg/m2 and carboplatin AUC 5 mg/mL/min or cisplatin 75 mg/m2 followed by maintenance pemetrexed. Randomization was stratified by PD-L1 TPS (<1% vs ≥1%), platinum (carboplatin vs cisplatin), and smoking status (current/former vs never). Response was assessed by RECIST v1.1 per blinded, independent central review. OS and PFS were primary endpoints.

Results: 616 pts were randomized (pembro-combination, n=410; placebo-combination, n=206). At data cutoff, median follow-up was 18.7 months. At baseline, 19% of pts had liver metastases and 18% had brain metastases. HRs for OS and PFS favored the pembro-combination vs placebo-combination across all groups, and were similar for pts with/without liver or brain metastases (Table).

Conclusion: Pembro plus pemetrexed-platinum provided superior outcomes vs chemotherapy alone irrespective of liver or brain metastases in pts with untreated metastatic nonsquamous NSCLC. Benefit was observed in pts with brain or liver metastases, for whom prognosis is historically poor.