Lenvima-Keytruda Combination May Show ‘Promising Antitumor Activity’ in Advanced Colorectal Cancer

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More than half of patients with previously treated advanced colorectal cancer who were treated with Lenvima and Keytruda were alive at six months while maintaining a manageable safety profile.

Treatment with Lenvima (lenvatinib) plus Keytruda (pembrolizumab) may benefit some patients with previously treated advanced colorectal cancer, according to findings from a study presented at the virtual 2021 ASCO Annual Meeting.

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

Keytruda, which is a standard care therapy across multiple cancer types, previously showed disease progression when followed by fluoropyrimidine, oxaliplatin and irinotecan. Previous data have also focused on the effectiveness of Lenvima.

“(Lenvima), an antigenic multi-kinase inhibitor, has shown efficacy in several solid tumors and is approved for the treatment of thyroid cancer, renal cell carcinoma and hepatocellular carcinoma,” the study authors wrote in the abstract. “The combination of (Lenvima) and (Keytruda) may lead to dual immunomodulatory effects and has shown promising antitumor activity and acceptable safety profile in patients with other solid tumors.”

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

Keytruda was administered as a 200-milligram dose every three weeks, and Lenvima was given orally as a 20-milligram dose once a day. Both treatments were administered for up to 35 cycles or until disease progression, unacceptable side effects or withdrawal of consent from the study. Treatment with Lenvima could continue beyond two years in patients who benefitted.

Researchers focused on certain factors including safety/tolerability, overall response rate (ORR; the percentage of patients with partial or complete responses to treatment), duration of response (the time a tumor continues to respond to therapy without cancer spread or growth), disease control rate (patients with stable or shrunken disease over time), overall survival (OS; period of time from diagnosis or treatment initiation when patients with cancer are still alive) and progression-free survival (PFS; time during and after treatment when patients with cancer live without disease worsening). Responses to the treatment were assessed every nine 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%, all of which were partial responses.

“Twenty-five percent of patients experienced stable disease, while 38% (had) progressive disease. The median duration of response was not reached,” Gomez-Roca said.

The six-month PFS rate was 31% (median, 2.3 months) with a six-month OS rate of 62% (median, 7.5 months).

All patients reported one or more treatment-related side effects, with the most common being high blood pressure (44%) and decreased appetite (31%). Severe or life-threatening side effects occurred in 47% of patients.

“There was one fatal treatment-related (side effect) due to intestinal perforation (loss of continuity of the bowel wall), and three patients discontinued treatment due to treatment-related (side effects) as increased liver enzymes, ischemic stroke and fat and intestinal perforation,” Gomez-Roca explained. “Fourteen patients experienced immune-mediated adverse events including hypothyroidism (or underactive thyroid) and hyperthyroidism (or overactive thyroid). There were no infusion reactions.”

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