Project Description

Oral Abstract Presentation
Selected by the 2020 Annual Meeting Scientific Program Committee
Type: Oral Abstract Presentation
Presenter: Thierry Andre, MD
Presented: May 30, 2020
Abstract ref: LBA4
Subtitles/Captions:

Authors:
Thierry Andre, Kai-Keen Shiu, Tae Won Kim, Benny Vittrup Jensen, Lars Henrik Jensen, Cornelis J. A. Punt, Denis Michel Smith, Rocio Garcia-Carbonero, Manuel Benavides, Peter Gibbs, Christelle De La Fouchardiere, Fernando Rivera, Elena Elez, Johanna C. Bendell, Dung T. Le, Takayuki Yoshino, Ping Yang, Mohammed Zulfiqar Husain Farooqui, Patricia Marinello, Luis A. Diaz; Sorbonne University and Saint-Antoine Hospital, Paris, France; University College London Hospital NHS Foundation Trust, London, United Kingdom; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Oncology, Herlev Hospital, Herlev, Denmark; Danish Colorectal Cancer Center South, Vejle University Hospital, Vejle, Denmark; Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Medical Oncology, Bordeaux University Hospital, Bordeaux, France; Hospital Universitario 12 de Octubre, Madrid, Spain; Hospital Universitario Regional y Virgen de la Victoria, Málaga, Spain; Royal Melbourne Hospital, Melbourne, Australia; Leon Berard Cancer Centre, Lyon, France; Hospital Universitario Marqués de Valdecilla, Santander, Spain; Medical Oncology Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; National Cancer Center Hospital East, Kashiwa, Japan; MSD China, Beijing, China; Merck & Co., Inc., Kenilworth, NJ; Memorial Sloan Kettering Cancer Center, New York, NY

Abstract Disclosures

Research Funding:
Merck & Co., Inc.

Background:
KEYNOTE-177 (NCT02563002) is a phase 3, randomized open-label study evaluating the efficacy and safety of pembrolizumab (pembro) versus standard of care chemotherapy ± bevacizumab or cetuximab (chemo) as first-line therapy for patients (pts) with microsatellite-instability high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). We present results of the final PFS analysis.

Methods:
A total of 307 pts with MSI-H/dMMR mCRC as determined locally and ECOG PS 0 or 1 were randomly assigned 1:1 to first-line pembro 200 mg Q3W for up to 2 years or investigator’s choice of mFOLFOX6 or FOLFIRI Q2W ± bevacizumab or cetuximab (chemo chosen prior to randomization). Treatment continued until PD, unacceptable toxicity, pt/investigator decision to withdraw, or completion of 35 cycles (pembro only). Patients receiving chemo could crossover to pembro for up to 35 cycles after confirmed PD. Primary end points were PFS (RECIST v1.1, central review) and OS. Key secondary end points included ORR (RECIST v1.1, central review), and safety. The data cutoff date for this interim analysis was Feb 19, 2020. The study will continue without changes to evaluate OS.

Results:
At data cutoff, 153 pts were randomized to pembro and 154 to chemo. Median (range) study follow-up was 28.4 mo (0.2-48.3) with pembro vs 27.2 mo (0.8-46.6) with chemo. Pembro was superior to chemo for PFS (median 16.5 mo vs 8.2 mo; HR 0.60; 95% CI, 0.45-0.80; P=0.0002). The 12- and 24-mo PFS rates were 55.3% and 48.3% with pembro vs 37.3% and 18.6% with chemo. Confirmed ORR was 43.8% vs 33.1%; median (range) duration of response was not reached (2.3+ to 41.4+) with pembro vs 10.6 mo (2.8 to 37.5+) with chemo. Grade 3-5 treatment related adverse event (AE) rates were 22% vs 66% for pembro vs chemo. One pt in the chemo arm died due to a treatment-related AE.

Conclusions:
Pembro provided a clinically meaningful and statistically significant improvement in PFS versus chemo as first-line therapy for pts with MSI-H/dMMR mCRC, with fewer treatment-related AEs observed and should be the new standard of care for these pts. Clinical trial information: NCT02563002.

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Oral Abstract Presentation
Selected by the 2020 Annual Meeting Scientific Program Committee
Type: Oral Abstract Presentation
Presenter: Thierry Andre, MD
Presented: May 30, 2020
Abstract ref: LBA4
Subtitles/Captions: