Project Description

Oral Abstract Presentation
Selected by the 2020 Annual Meeting Scientific Program Committee
Type: Oral Abstract Presentation
Presenter: Javier Cortes, MD, PhD
Presented: May 29, 2020
Abstract ref: 1000
Subtitles/Captions:

Authors: Javier Cortes, David W. Cescon, Hope S. Rugo, Zbigniew Nowecki, Seock-Ah Im, Mastura Md Yusof, Carlos Gallardo, Oleg Lipatov, Carlos Henrique Barrios, Esther Holgado, Hiroji Iwata, Norikazu Masuda, Marco Torregroza Otero, Erhan Gokmen, Sherene Loi, Zifang Guo, Jing Zhao, Gursel Aktan, Vassiliki Karantza, Peter Schmid; IOB Institute of Oncology, Quiron Group & Vall d´Hebron Institute of Oncology (VHIO), Madrid & Barcelona, Spain; Princess Margaret Cancer Centre, Toronto, ON, Canada; University of California San Francisco Comprehensive Cancer Center, San Francisco, CA; Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland; Seoul National University Hospital, Seoul, South Korea; Pantai Hospital, Kuala Lumpur, Malaysia; Arturo Lopez Perez Foundation, Santiago, Chile; Republican Clinical Oncology Dispensary of the Ministry of Public Health of Bashkortostan Republic, Ufa, Russian Federation; Centro de Hematologia e Oncologia, Porto Alegre, Brazil; Aichi Cancer Center Hospital, Nagoya, Japan; National Hospital Organization, Osaka National Hospital, Osaka, Japan; Oncomedica S.A., Monteria, Colombia; Ege University Medical Faculty, Izmir, Turkey; Peter MacCallum Cancer Institute, Melbourne, VIC, Australia; Merck & Co., Inc., Kenilworth, NJ; Barts Cancer Institute, Centre for Experimental Cancer Medicine, London, United Kingdom

Abstract Disclosures

Research Funding: Merck & Co., Inc.

Background: Pembrolizumab (pembro) monotherapy showed promising antitumor activity and manageable safety in patients (pts) with metastatic TNBC in KEYNOTE-012, -086 and -119. KEYNOTE-355 (ClinicalTrials.gov, NCT02819518) compared pembro + chemotherapy (chemo) vs placebo (pbo) + chemo for previously untreated locally recurrent inoperable or metastatic TNBC.

Methods: Pts with ≥6 mo DFI were randomized 2:1 to pembro + chemo (nab-paclitaxel; paclitaxel; or gemcitabine/carboplatin) or pbo + chemo for up to 35 administrations of pembro/pbo or until progression/intolerable toxicity. Pts were stratified by chemo type (taxane vs gemcitabine/carboplatin), PD-L1 status (CPS ≥1 vs <1), and prior (neo)adjuvant treatment with same-class chemo (yes vs no). Dual primary endpoints are PFS (RECIST v1.1, blinded independent central review) and OS by tumor PD-L1 expression (CPS ≥10 and ≥1) and in all pts. PFS was estimated using the Kaplan-Meier method. Stratified log-rank tests were used to assess treatment group differences. HR and 95% CIs were based on a stratified Cox regression model. AEs were monitored throughout the study and graded per NCI CTCAE v4.0.

Results: As of Dec 11 2019, median follow-up was 17.5 mo for pembro + chemo (n=566) and 15.5 mo for chemo (n=281). Pembro + chemo significantly improved PFS vs chemo alone in pts with CPS ≥10 tumors (Table), meeting one of the protocol-defined primary objectives. Although the boundary for a statistically significant benefit of pembro + chemo in pts with CPS ≥1 tumors was not met and formal testing in ITT was not performed, the pembro treatment effect increased with PD-L1 enrichment (Table). OS follow-up is ongoing. Grade 3-5 treatment-related AE rates were 68.1% with pembro + chemo (2 deaths) vs 66.9% with chemo (0 deaths); rates of grade 3-4 immune-mediated AEs and infusion reactions were 5.5% vs 0%. Clinical trial information: NCT02819518.

Conclusion:Pembro combined with several chemo partners showed a statistically significant and clinically meaningful improvement in PFS vs chemo alone in pts with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1 (CPS ≥10). Pembro + chemo was generally well tolerated, with no new safety concerns.

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Oral Abstract Presentation
Selected by the 2020 Annual Meeting Scientific Program Committee
Type: Oral Abstract Presentation
Presenter: Javier Cortes, MD, PhD
Presented: May 29, 2020
Abstract ref: 1000
Subtitles/Captions: