Pembrolizumab monotherapy

In the phase III, open-label, international, randomized KEYNOTE-177 trial (NCT02563002), 307 patients with treatment-naïve MSI-H or dMMR metastatic colorectal cancer were randomly assigned in a 1:1 ratio to receive either pembrolizumab (200 mg every 3 weeks) or chemotherapy (FOLFIRI or modified FOLFOX-6 with or without bevacizumab or cetuximab).[68]

In the phase III, open-label, international, randomized KEYNOTE-177 trial (NCT02563002), 307 patients with treatment-naïve MSI-H or dMMR metastatic colorectal cancer were randomly assigned in a 1:1 ratio to receive either pembrolizumab (200 mg every 3 weeks) or chemotherapy (FOLFIRI or modified FOLFOX-6 with or without bevacizumab or cetuximab).[68]

The median PFS was 16.5 months for patients who received pembrolizumab and 8.2 months for patients who received chemotherapy (HR, 0.60; 95% CI, 0.45–0.80; P = .0002).[68][Level of evidence A3]

In the phase III, open-label, international, randomized KEYNOTE-177 trial (NCT02563002), 307 patients with treatment-naïve MSI-H or dMMR metastatic colorectal cancer were randomly assigned in a 1:1 ratio to receive either pembrolizumab (200 mg every 3 weeks) or chemotherapy (FOLFIRI or modified FOLFOX-6 with or without bevacizumab or cetuximab).[68]

The PFS in prespecified subgroups showed HRs that favored the pembrolizumab arm, except in patients with KRAS or NRAS variants.

In the phase III, open-label, international, randomized KEYNOTE-177 trial (NCT02563002), 307 patients with treatment-naïve MSI-H or dMMR metastatic colorectal cancer were randomly assigned in a 1:1 ratio to receive either pembrolizumab (200 mg every 3 weeks) or chemotherapy (FOLFIRI or modified FOLFOX-6 with or without bevacizumab or cetuximab).[68]

The objective response rate was 43.8% in the pembrolizumab arm and 33.3% in the chemotherapy arm. The median duration of response was not reached in the pembrolizumab arm (range, 2.3–41.4 months) and was 10.6 months in the chemotherapy arm (range, 2.8–37.5 months).

In the phase III, open-label, international, randomized KEYNOTE-177 trial (NCT02563002), 307 patients with treatment-naïve MSI-H or dMMR metastatic colorectal cancer were randomly assigned in a 1:1 ratio to receive either pembrolizumab (200 mg every 3 weeks) or chemotherapy (FOLFIRI or modified FOLFOX-6 with or without bevacizumab or cetuximab).[68]

Grade 3 or higher adverse events occurred in 56% of patients who received pembrolizumab (with 9% experiencing grade 3 or higher infusion-related adverse events), compared with 78% of patients who received chemotherapy.

In the phase III, open-label, international, randomized KEYNOTE-177 trial (NCT02563002), 307 patients with treatment-naïve MSI-H or dMMR metastatic colorectal cancer were randomly assigned in a 1:1 ratio to receive either pembrolizumab (200 mg every 3 weeks) or chemotherapy (FOLFIRI or modified FOLFOX-6 with or without bevacizumab or cetuximab).[68]

A final review of OS, presented in abstract form, showed that median OS was not reached in the pembrolizumab arm and was 36.7 months in the chemotherapy arm (HR, 0.74; 95% CI, 0.53–1.03; P = .0359).[69]