Abstract | BACKGROUND: METHODS: RESULTS: At the second interim analysis, after a median follow-up (from randomization to data cutoff) of 32.4 months (range, 24.0 to 48.3), pembrolizumab was superior to chemotherapy with respect to progression-free survival (median, 16.5 vs. 8.2 months; hazard ratio, 0.60; 95% confidence interval [CI], 0.45 to 0.80; P = 0.0002). The estimated restricted mean survival after 24 months of follow-up was 13.7 months (range, 12.0 to 15.4) as compared with 10.8 months (range, 9.4 to 12.2). As of the data cutoff date, 56 patients in the pembrolizumab group and 69 in the chemotherapy group had died. Data on overall survival were still evolving (66% of required events had occurred) and remain blinded until the final analysis. An overall response (complete or partial response), as evaluated with Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, was observed in 43.8% of the patients in the pembrolizumab group and 33.1% in the chemotherapy group. Among patients with an overall response, 83% in the pembrolizumab group, as compared with 35% of patients in the chemotherapy group, had ongoing responses at 24 months. Treatment-related adverse events of grade 3 or higher occurred in 22% of the patients in the pembrolizumab group, as compared with 66% (including one patient who died) in the chemotherapy group. CONCLUSIONS:
Pembrolizumab led to significantly longer progression-free survival than chemotherapy when received as first-line therapy for MSI-H-dMMR metastatic colorectal cancer, with fewer treatment-related adverse events. (Funded by Merck Sharp and Dohme and by Stand Up to Cancer; KEYNOTE-177 ClinicalTrials.gov number, NCT02563002.).
|
Authors | Thierry André, Kai-Keen Shiu, Tae Won Kim, Benny Vittrup Jensen, Lars Henrik Jensen, Cornelis Punt, Denis Smith, Rocio Garcia-Carbonero, Manuel Benavides, Peter Gibbs, Christelle de la Fouchardiere, Fernando Rivera, Elena Elez, Johanna Bendell, Dung T Le, Takayuki Yoshino, Eric Van Cutsem, Ping Yang, Mohammed Z H Farooqui, Patricia Marinello, Luis A Diaz Jr, KEYNOTE-177 Investigators |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 383
Issue 23
Pg. 2207-2218
(12 03 2020)
ISSN: 1533-4406 [Electronic] United States |
PMID | 33264544
(Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2020 Massachusetts Medical Society. |
Chemical References |
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents, Immunological
- Biomarkers, Tumor
- Immune Checkpoint Inhibitors
- pembrolizumab
- Fluorouracil
|
Topics |
- Adult
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal, Humanized
(adverse effects, therapeutic use)
- Antineoplastic Agents, Immunological
(adverse effects, therapeutic use)
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Biomarkers, Tumor
(genetics)
- Brain Neoplasms
- Colorectal Neoplasms
(drug therapy, genetics, mortality)
- Female
- Fluorouracil
(therapeutic use)
- Humans
- Immune Checkpoint Inhibitors
(adverse effects, therapeutic use)
- Kaplan-Meier Estimate
- Male
- Microsatellite Instability
- Middle Aged
- Mutation
- Neoplastic Syndromes, Hereditary
- Progression-Free Survival
|
|
Join CureHunter, for free Research Interface BASIC access!
Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease.
Find out why thousands of doctors, pharma researchers and patient activists
around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!
|