![]() Furthermore, pembro provided a clinically meaningful improvement in PFS2 for patients with MSI-H/dMMR mCRC. Conclusions: Pembro provided a statistically significant improvement in PFS vs chemo as first-line therapy for patients with MSI-H/dMMR mCRC, with fewer TRAEs observed. HRQoL scores were improved with pembro vs chemo. There were no grade 5 TRAEs in the pembro arm and 1 grade 5 intestinal perforation in the chemo arm. Grade ≥3 treatment related adverse event (TRAE) rates were 22% vs 66% for pembro vs chemo. PFS2 was longer with pembro vs chemo (median not reached vs 23.5 mo ). Confirmed ORR was 43.8% vs 33.1% median (range) DOR was not reached (2.3+ to 41.4+) with pembro vs 10.6 mo (2.8 to 37.5+) with chemo. The 12- and 24-mo PFS rates were 55.3% and 48.3% with pembro vs 37.3% and 18.6% with chemo. Results: At data cutoff a total of 307 patients were randomized (153 to pembro, 154 to chemo). Exploratory endpoints included duration of response (DOR), PFS2 (time from randomization to progression on next line of therapy or any cause death), and health-related quality of life (HRQoL). Secondary end points included ORR (RECIST v1.1, central review) and safety. Primary end points were PFS (RECIST v1.1, central review) and OS. Patients receiving chemo could crossover to pembro for up to 35 cycles after confirmed PD. Treatment continued until progression, unacceptable toxicity, patient/investigator decision to withdraw, or completion of 35 cycles (pembro only). Methods: Patients with locally-determined MSI-H/dMMR mCRC and ECOG PS 0 or 1 were randomized 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 (chosen before randomization). We present results of the final PFS analysis and analysis of PFS2. Patients with these mutations face a poorer prognosis as well as a greater risk of death than colorectal cancer that is microsatellite stable.Background: KEYNOTE-177 (NCT02563002) evaluated the antitumor activity of pembrolizumab (pembro) vs chemotherapy ± bevacizumab or cetuximab (chemo) as first-line therapy for patients with microsatellite-instability high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). High MSI or MMR deficiency is observed in approximately 4% of metastatic colorectal cancer patients, and about 450 patients in England will become eligible for Keytruda treatment. We are pleased, therefore, to be able to recommend for routine use in the NHS,” he added.Ĭells that are mismatch repair (MMR) deficient often have many DNA mutations, and are commonly found in colorectal, gastrointestinal and endometrial cancer. “It also works in a different way to current standard care with chemotherapy and the committee heard that people appreciated its faster and less frequent administration, and preferable adverse effects compared with chemotherapy. has shown the potential to extend the lives of hundreds of people with this form of colorectal cancer,” said Meindert Boysen, deputy chief executive and director of the Centre for Health Technology Evaluation at NICE. "There are currently no specific treatments for untreated metastatic colorectal cancer with high microsatellite instability or mismatch repair deficiency. Merck & Co added in its own statement that the KEYNOTE-177 trial is still ongoing to assess the impact on patients’ overall survival with Keytruda treatment. In a statement, NICE said that although the clinical trial evidence showed an increase in progression-free survival for Keytruda in these patients, its independent appraisal committee said the long-term evidence is ‘limited’.Īs a result, NICE recommends that Keytruda treatment should be stopped at two years if there is no evidence that a person’s disease has progressed. In addition, 48.3% of patients receiving Keytruda lived 24 or months without their cancer progressing, compared with 18.6% in the chemotherapy group. In the phase 3 KEYNOTE-177 trial, Keytruda was found to slow or halt progression of metastatic MSI-H/dMMR colorectal cancers for a median of 16.5 months versus 8.2 months for chemotherapy. The draft guidance recommends Merck & Co’s – known as MSD outside the US and Canada – Keytruda (pembrolizumab) for the treatment of patients with previously untreated metastatic colorectal cancers with high levels of microsatellite instability (MSI-H) or DNA mismatch repair deficiency (dMMR). The UK’s National Institute for Health and Care Excellence (NICE) has recommended Keytruda for NHS use as a first-line treatment for colorectal cancer patients with rare mutations.
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