Overall Survival Rates in Advanced Colorectal Cancer May be Improved with Lenvatinib Plus Pembrolizumab

lenvatinib plus pembrolizumab elicited a response in some patients with advanced colorectal cancer.

lenvatinib (Lenvima) plus pembrolizumab (Keytruda) elicited a response in some patients with advanced colorectal cancer, according to findings from the LEAP-005 study presented at the virtual 2021 ASCO Annual Meeting.

“Patients with previously treated advanced non-MSI-high or (proficient mismatch repair) colorectal cancer, lenvatinib plus pembrolizumab demonstrated promising antitumor activity and a manageable safety profile,” said lead study author Carlos A. Gomez-Roca, MD, cancer specialist at the Institut Universitaire du Cancer de Toulouse in France, during the presentation.

The nonrandomized, open-label, phase 2 study included 32 adult patients (median age, 56 years; 19% women; 91% received two prior lines of treatment) with advanced colorectal cancer. Eligible patients were also previously treated with oxaliplatin and irinotecan as separate lines of therapy.

“Pembrolizumab was administered at a dose of 200 milligrams every 3 weeks, and lenvatinib (was) received orally once a day at a dose of 20 milligrams,” Gomez-Roca explained, noting that they were administered for up to 35 cycles or until disease progression, unacceptable toxicity or withdrawal of consent. Treatment with lenvatinib could continue beyond 2 years in patients with clinical benefit.

The primary endpoints of this study included safety/tolerability and overall response rate. Secondary endpoints included duration of response, disease control rate, overall survival and progression-free survival. Responses to the treatment were assessed every 9 weeks until 54 weeks, when follow-up was conducted every 12 weeks until 102 weeks. Once that occurred, follow-up was conducted every 24 weeks.

The median treatment cutoff was 10.6 months. Patients had an overall response rate of 22% (95% CI, 9-40), all of which were partial responses.

“Of note, responders had PD-L1-positive tumors by CPS score equal or more than 1,” Gomez-Roca said. “Twenty-five percent of patients experienced stable disease, while 38% (had) progressive disease. The median duration of response was not reached.”

The 6-month progression free survival rate was 31% (median, 2.3 months; 95% CI, 2-5.2) with a 6-month overall survival rate of 62% (median, 7.5 months; 95% CI, 3.9-not reached). 

All patients reported one or more treatment-related adverse events, with the most common being hypertension (44%) and decreased appetite (31%). Grade 3 and 4 treatment-related adverse events occurred in 47% of patients.

“There was one fatal treatment-related adverse event due to intestinal perforation, and three patients discontinued treatment due to treatment-related (adverse events) as increased liver enzymes, ischemic stroke and fat and intestinal perforation,” Gomez-Roca explained. “Fourteen patients experienced immune-mediated adverse events including hypothyroidism and hyperthyroidism. There were no infusion reactions.”

Based on this data, enrollment in the colorectal cancer cohort has been expanded to 100 patients, Gomez-Roca said.

Gomez-Roca CA, Yanez E, Im S-A, et al. LEAP-005: A phase 2 multicohort study of lenvatinib plus pembrolizumab in patients with previously treated selected solid tumors—Results from the colorectal cancer cohort. Presented at: 2021 ASCO Annual Meeting; June 4-8, 2021; Virtual. Abstract 3564.

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