Patients With Advanced CRC May Experience Survival Benefit With Lenvatinib Plus Pembrolizumab Combo

Phase 2 data presented at the 2021 ASCO Annual Meeting indicate that more than half of patients with previously treated advanced colorectal cancer who were treated with pembrolizumab plus lenvatinib were alive at 6 months.

Data from the LEAP-005 trial (NCT03797326) presented at the 2021 ASCO Annual Meeting regarding lenvatinib (Lenvima) plus pembrolizumab (Keytruda) in patients with previously treated advanced colorectal cancer (CRC) reveal certain patients may benefit from therapy, with high rates of overall and progression-free survival (PFS) noted at 6 months. 

“For 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,” lead study author Carlos A. Gomez-Roca, MD, cancer specialist at the Institut Universitaire du Cancer de Toulouse in France, said 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 CRC. 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 PFS 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 CRC 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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