Abstract CT043: 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
Authors: Garassino Marina C. , Gadgeel Shirish , Esteban Emilio , Felip Enriqueta , Speranza Giovanna , Angelis Flávia De , Domine Manuel , Clingan Philip , Hochmair Maximilian J. , Powell Steven F. , Cheng Susanna Y.-S. , Bischoff Helge G. , Peled Nir , Grossi Francesco , Jennens Ross R. , Reck Martin , Hui Rina , Garon Edward B. , Boyer Michael , Rubio-Viqueira Belén , Novello Silvia , Kurata Takayasu , Gray Jhanelle E. , Cardellino Anna , Yang Jing , Pietanza M. Catherine , Rodríguez-Abreu Delvys 
Published: August 2019

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&lt;0.001) and PFS (HR, 0.52; 95% CI, 0.43-0.64; P&lt;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 (&lt;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.

PFSOSN*Median, mo (95% CI)HR(95% CI)Median, mo (95% CI)HR(95% CI)Pts With Liver MetastasesPembro-combination666.1 (4.7-8.5)0.52 (0.34-0.81)12.6 (8.1-19.1)0.62 (0.39-0.98)Placebo-combination493.4 (2.8-4.7)6.6 (4.6-7.6)Pts Without Liver MetastasesPembro-combination3449.2 (8.8-11.0)0.48 (0.39-0.59)23.7 (20.1-25.9)0.58 (0.45-0.74)Placebo-combination1575.4 (4.9-6.7)13.2 (10.0-16.4)Pts With Brain MetastasesPembro-combination736.9 (5.4-11.0)0.42 (0.27-0.67)19.2 (15.0-25.9)0.41 (0.24-0.67)Placebo-combination354.7 (2.2-5.5)7.5 (4.6-10.0)Pts Without Brain MetastasesPembro-combination3379.2 (8.3-10.9)0.48 (0.39-0.59)22.4 (19.7-25.4)0.59 (0.46-0.75)Placebo-combination1714.9 (4.7-5.9)12.1 (9.1-15.0)*25 patients had both brain and liver metastases.

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Citation Format: Marina C. Garassino, Shirish Gadgeel, Emilio Esteban, Enriqueta Felip, Giovanna Speranza, Flávia De Angelis, Manuel Domine, Philip Clingan, Maximilian J. Hochmair, Steven F. Powell, Susanna Y.-S. Cheng, Helge G. Bischoff, Nir Peled, Francesco Grossi, Ross R. Jennens, Martin Reck, Rina Hui, Edward B. Garon, Michael Boyer, Belén Rubio-Viqueira, Silvia Novello, Takayasu Kurata, Jhanelle E. Gray, Anna Cardellino, Jing Yang, M. Catherine Pietanza, Delvys Rodríguez-Abreu. 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]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT043.