4580 - Outcomes with pembrolizumab (pembro) monotherapy in patients (pts) with PD-L1–positive NSCLC with brain metastases: Pooled analysis of KEYNOTE-001, -010, -024, and -042

Background

Prognosis is historically poor for pts with NSCLC with brain metastases. We present a pooled analysis from 4 clinical trials that evaluated outcomes in pts with PD-L1–positive NSCLC with stable brain metastases at baseline treated with pembro vs chemotherapy (chemo).

Methods

This post hoc analysis pooled data for pts with previously treated or untreated PD-L1–positive (PD-L1 TPS ≥1%) advanced NSCLC in KEYNOTE-001 (NCT01295827), KEYNOTE-010 (NCT01905657), KEYNOTE-024 (NCT02142738), and KEYNOTE-042 (NCT02220894) assigned to pembro (2 mg/kg, 10 mg/kg, or 200 mg Q3W, or 10 mg/kg Q2W) vs docetaxel (for previously treated NSCLC) or platinum-based chemo (for previously untreated NSCLC) Q3W. All studies included pts with stable brain metastases (ie, no symptoms or intracranial progression). Response (systemic, including in brain) was assessed per RECIST v1.1 by blinded, independent central review.

Results

3170 pts were included, 293 with and 2877 without baseline brain metastases; median (range) follow-up at data cutoff was 18.4 (0.5–43.7) mo and 12.6 (0.1–42.5) mo, respectively. HRs for OS and PFS were less than 1 with pembro vs chemo irrespective of baseline brain metastasis status (Table). Objective response rates were similar with pembro vs chemo but duration of response was longer with pembro. Fewer treatment-related AEs occurred with pembro vs chemo both in pts with brain metastases (66% vs 84%) and without (67% vs 88%); immune-mediated AEs and infusion reactions occurred in 21% vs 9%, respectively, with brain metastases and 25% vs 8% without.Table:

1482O

+, response ongoing at data cutoff; NR, not reached.

Conclusions

Pembro improved clinical outcomes and was well-tolerated vs chemo in pts with stable brain metastases, and provided similar outcomes in pts with and without brain metastases. Pembro is standard treatment in pts with advanced PD-L1–positive NSCLC, irrespective of brain metastases at baseline.

Clinical trial identification

NCT01295827; NCT01905657; NCT02142738; NCT02220894.

Editorial acknowledgement

Sheri Arndt, PharmD, of C4 MedSolutions, LLC (Yardley, PA, USA), a CHC Group company, funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

A.S. Mansfield: Honoraria (institution): AbbVie; Honoraria (institution): BMS; Honoraria (institution): Genentech; Research grant / Funding (institution): NIH; Honoraria (institution): Novartis; Honoraria (institution): Verily; Officer / Board of Directors, Non-remunerated activity/ies, unremunerated medical society/research group/foundation leadership as board member: Mesothelioma Applied Research Foundation. R.S. Herbst: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Merck; Advisory / Consultancy, consultant/advisory board member: AbbVie; Advisory / Consultancy, consultant/advisory board member: AstraZeneca; Advisory / Consultancy, consultant/advisory board member: Biodesix; Advisory / Consultancy, consultant/advisory board member: BMS; Advisory / Consultancy, consultant/advisory board member: Eli Lilly; Advisory / Consultancy, consultant/advisory board member: EMD Serono; Advisory / Consultancy, consultant/advisory board member: Genentech/Roche; Advisory / Consultancy, consultant/advisory board member: Heat Biologics; Advisory / Consultancy, consultant/advisory board member: Infinity Pharmaceuticals ; Advisory / Consultancy, consultant/advisory board member: Loxo Oncology; Advisory / Consultancy, consultant/advisory board member: Merck; Advisory / Consultancy, consultant/advisory board member: Nektar Therapeutics; Advisory / Consultancy, consultant/advisory board member: Neon Therapeutics; Advisory / Consultancy, consultant/advisory board member: NextCure; Advisory / Consultancy, consultant/advisory board member: Novartis; Advisory / Consultancy, consultant/advisory board member: Pfizer; Advisory / Consultancy, consultant/advisory board member: Sanofi; Advisory / Consultancy, consultant/advisory board member: Seattle Genetics; Advisory / Consultancy, consultant/advisory board member: Spectrum Pharmaceuticals; Advisory / Consultancy, consultant/advisory board member: Symphogen; Advisory / Consultancy, consultant/advisory board member: Tesaro; Advisory / Consultancy, consultant/advisory board member: ARMO BioSciences; Advisory / Consultancy, consultant/advisory board member: Genmab; Advisory / Consultancy, consultant/advisory board member: Tocagen; Advisory / Consultancy, board member (nonexecutive/independent): Junshi Biosciences. Commercial research grants from AstraZeneca, Eli Lilly, and Merck; consultant/advisory board member for AbbVie, AstraZeneca, Biodesix, BMS, Eli Lilly, EMD Serono, Genentech/Roche, Heat Biologics, Infinity Pharmaceuticals, Loxo Oncology, Merck, Nektar Therapeutics, Neon Therapeutics, NextCure, Novartis, Pfizer, Sanofi, Seattle Genetics, Shire, Spectrum Pharmaceuticals, Symphogen, Tesaro, ARMO BioSciences, Genmab, and Tocagen; board member (nonexecutive/independent) for Junshi Biosciences. G. Castro Jr: Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Yuhan; Speaker Bureau / Expert testimony: TEVA; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono. R. Hui: Honoraria (institution), Advisory / Consultancy: MSD; Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: BMS. N. Peled: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), grants, personal fees, and honoraria for serving as an advisor: AstraZeneca; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), grants, personal fees, and honoraria for serving as an advisor: Boehringer Ingelheim; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), grants, personal fees, and honoraria for serving as an advisor: BMS; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), grants, personal fees, and honoraria for serving as an advisor: Eli Lilly; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), grants, personal fees, and honoraria for serving as an advisor: MSD; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), grants, personal fees, and honoraria for serving as an advisor: Novartis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), grants, personal fees, and honoraria for serving as an advisor: Pfizer; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), grants, personal fees, and honoraria for serving as an advisor: Roche; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), grants, personal fees, and honoraria for serving as an advisor: NovellusDx; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), grants, personal fees, and honoraria for serving as an advisor: FMI; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), grants, personal fees, and honoraria for serving as an advisor: Gaurdant360. D. Kim: Research grant / Funding (institution): Alpha Biopharma; Research grant / Funding (institution): AstraZeneca/MedImmune; Research grant / Funding (institution): Hanmi; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Merus; Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): ONO Pharmaceutical; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): TP Therapeutics; Research grant / Funding (institution): Xcovery; Research grant / Funding (institution): Yuhan. S. Novello: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD. M. Satouchi: Honoraria (institution), Research grant / Funding (institution): AstraZeneca; Honoraria (institution), Research grant / Funding (institution): MSD; Honoraria (institution), Research grant / Funding (institution): Chugai; Honoraria (institution): Taiho; Honoraria (institution), Research grant / Funding (institution): Pfizer; Honoraria (institution), Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (institution), Research grant / Funding (institution): BMS; Honoraria (institution), Research grant / Funding (institution): Ono; Honoraria (institution), Research grant / Funding (institution): Novartis; Honoraria (institution), Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Ignyta. Y. Wu: Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution): Eli Lilly; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (institution): Pierre Fabre; Honoraria (institution): Pfizer; Honoraria (institution): Sanofi; Advisory / Consultancy: Merck ; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim. E.B. Garon: Advisory / Consultancy: Dracen; Advisory / Consultancy: EMD Serono; Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Neon Therapeutics; Research grant / Funding (institution): Iovance Biotherapeutics; Research grant / Funding (institution): Dynavax; Research grant / Funding (institution): Mirati Therapeutics. M. Reck: Honoraria (institution), honoraria for consulting and lectures: Amgen; Honoraria (institution), honoraria for consulting and lectures: AstraZeneca; Honoraria (institution), honoraria for consulting and lectures: BMS; Honoraria (institution), honoraria for consulting and lectures: Boehringer Ingelheim; Honoraria (institution), honoraria for consulting and lectures: Celgene; Honoraria (institution), honoraria for consulting and lectures: Merck; Honoraria (institution), honoraria for consulting and lectures: MSD; Honoraria (institution), honoraria for consulting and lectures: Eli Lilly; Honoraria (institution), honoraria for consulting and lectures: Pfizer; Honoraria (institution), honoraria for consulting and lectures: AbbVie; Honoraria (institution), honoraria for consulting and lectures: Roche; Honoraria (institution), honoraria for consulting and lectures: Novartis. A.G. Robinson: Research grant / Funding (institution): BMS; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Roche; Research grant / Funding (institution): AstraZeneca. A. Samkari: Full / Part-time employment, employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.: Merck Sharp & Dohme Corp. B. Piperdi: Full / Part-time employment, employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and owns stock in Merck & Co., Inc., Kenilworth, NJ, USA.: Merck Sharp & Dohme Corp. V. Ebiana: Full / Part-time employment, employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.: Merck Sharp & Dohme Corp. J. Lin: Full / Part-time employment, employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. : Merck Sharp & Dohme Corp. T.S.K. Mok: grants or research support from AstraZeneca, BMS, Clovis Oncology, Merck Sharp & Dohme, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, and XCovery; speakers\' fees from AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, BMS, Taiho, and Takeda Oncology; honoraria from AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Merck Serono, Merck Sharp & Dohme, Novartis, SFJ Pharmaceuticals, ACEA Biosciences, Inc., Vertex Pharmaceuticals, BMS, OncoGenex Pharmaceuticals, Inc., Celgene, Ignyta, Inc., Fishawack Facilitate Ltd, Takeda Oncology, and Janssen; major stockholder in Sanomics Ltd.; advisory board member for AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Clovis Oncology, Merck Serono, Merck Sharp & Dohme, Novartis, SFJ Pharmaceuticals, ACEA Biosciences, Inc., Vertex Pharmaceuticals, BMS, geneDecode Co., Ltd., OncoGenex Technologies Inc., Celgene, Ignyta, Inc., Cirina, Fishawack Facilitate Ltd., Janssen, Takeda, and ChiMed; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Merck Sharp & Dohme; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): SFJ Pharmaceuticals; Research grant / Funding (institution): XCovery; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Roche/Genentech; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eli Lilly; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Taiho; Speaker Bureau / Expert testimony: Takeda Oncology; Honoraria (self): AstraZeneca; Honoraria (self): Roche/Genentech; Honoraria (self): Pfizer; Honoraria (self): Eli Lilly; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Merck Serono; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Novartis; Honoraria (self): SFJ Pharmaceuticals; Honoraria (self): ACEA Biosciences, Inc.; Honoraria (self): Vertex Pharmaceuticals; Honoraria (self): BMS; Honoraria (self): OncoGenex Pharmaceuticals, Inc.; Honoraria (self): Celgene; Honoraria (self): Ignyta, Inc.; Honoraria (self): Fishawack Facilitate Ltd; Honoraria (self): Takeda Oncology; Honoraria (self): Janssen; Shareholder / Stockholder / Stock options: Sanomics Ltd.; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Novartis; Advisory / Consultancy: SFJ Pharmaceuticals; Advisory / Consultancy: ACEA Biosciences, Inc.; Advisory / Consultancy: Vertex Pharmaceuticals; Advisory / Consultancy: BMS; Advisory / Consultancy: geneDecode Co.; Advisory / Consultancy: OncoGenex Technologies Inc.; Advisory / Consultancy: Celgene; Advisory / Consultancy: Ignyta, Inc., Advisory / Consultancy: Cirina; Advisory / Consultancy: Fishawack Facilitate Ltd.; Advisory / Consultancy: Janssen; Advisory / Consultancy: Takeda;Advisory / Consultancy: ChiMed.