#Keynote 177 trial
Clinical trial information: NCT02563002.KENILWORTH, N.J.-( BUSINESS WIRE)-Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced today that the European Commission has approved KEYTRUDA, Merck’s anti-PD-1 therapy, as a monotherapy for the first-line treatment of adult patients with metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. Together these data confirm pembro as a new standard-of-care in the 1L for pts with MSI-H/dMMR mCRC. Conclusions: As 1L therapy for pts with MSI-H/dMMR mCRC, pembro vs chemo provides statistically superior PFS with fewer TRAEs, and is associated with a trend toward reduced mortality that did not meet statistical significance likely due to the high crossover rate from chemo to anti-PD1/PD-L1 therapies. Treatment-related adverse events (TRAEs) occurred in 79.7% vs 98.6% of pts 21.6% vs 66.4%, respectively, had grade ≥3 TRAEs. At final analysis, median PFS was 16.5 mo vs 8.2 mo (HR 0.59 95% CI, 0.45-0.79), but was not formally tested per analysis plan.
Pembro vs chemo met the prespecified criteria for PFS superiority at IA2. Sensitivity analysis by the rank-preserving structure failure time model and inverse probability of censoring weighting showed OS HRs of 0.66 (95% CI 0.42-1.04) and 0.77 (95% CI 0.44-1.38), respectively. The HR for OS favored pembro vs chemo with a trend toward reduction in the risk of death (HR 0.74 95% CI, 0.53-1.03 P=0.0359 median not reached vs 36.7 mo) this difference did not reach statistical significance. 56 (36%) pts crossed over from chemo to pembro, with 37 more receiving anti-PD-1/PD-L1 therapies off study (60% effective crossover rate in the ITT). Data cut-off for final analysis was Feb 19, 2021. Sensitivity analyses to adjust for crossover effect were performed. For OS significance, the p-value had to meet a prespecified α of 0.0246 (one-sided). Secondary end points included ORR, duration of response (DOR) (RECIST v1.1, central review), and safety. Primary end points were OS and PFS (RECIST v1.1, central review). Pts receiving chemo could crossover to pembro for up to 35 cycles after confirmed PD. Treatment continued until PD, unacceptable toxicity, pt/investigator decision to withdraw, or completion of 35 cycles (pembro only). Methods: A total of 307 pts with MSI-H/dMMR mCRC and ECOG PS 0 or 1 were randomized 1:1 to 1L pembro 200 mg Q3W for up to 2y or investigator’s choice of mFOLFOX6 or FOLFIRI Q2W ± bevacizumab or cetuximab. We present results of the final analysis of OS, 12 months after IA2. The study continued to final analysis of overall survival (OS), planned after 190 OS events or 12 months after IA2, whichever occurred first. Albans, Australia Centre Léon Bérard, Lyon, France Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain Vall d‘Hebron Institute of Oncology, Barcelona, Spain Sarah Cannon Research Institute/Tennessee Oncology PLLC, Nashville, TN The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD National Cancer Center Hospital East, Kashiwa, Japan MSD China, Shanghai, China Merck & Co., Inc., Kenilworth, NJ Memorial Sloan Kettering Cancer Center, New York, NYī ackground: In the phase III, randomized open-label KEYNOTE-177 (NCT02563002) study 1L pembrolizumab (pembro) versus chemotherapy (chemo) provided superior progression-free survival (PFS) at second interim analysis (IA2) in patients (pts) with MSI-H/dMMR mCRC. Sorbonne Université and Hôpital-Saint Antoine, Paris, France University College Hospital, NHS Foundation Trust, London, United Kingdom Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea Herlev and Gentofte Hospital, Herlev, Denmark University Hospital of Southern Denmark, Vejle, Denmark Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, Netherlands Bordeaux University Hospital, Bordeaux, France Hospital Universitario 12 de Octubre, Imas12, CNIO, UCM, Madrid, Spain Hospital Regional Universitario de Malaga, Málaga, Spain Western Health, St.
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