Keytruda Plus Mektovi and Avastin Associated With Survival Benefit in Metastatic Colon Cancer

The preliminary findings of a phase 2 study showed that more than half of the patients with microsatellite-stable, treatment-refractory metastatic colorectal cancer enrolled in the trial experienced a clinical benefit after receiving Keytruda (pembrolizumab), Mektovi (binimetinib) and Avastin (bevacizumab).

The data, which were presented at the 2022 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, also demonstrated that the treatment regimen was associated with a progression-free survival (time during and after treatment a patient lives with the disease without it getting worse) benefit not traditionally seen in the patient population.

In fact, the study authors noted that despite many Food and Drug Administration-approved therapies, long-term survival for this population is poor and responses to later lines of treatment are rather short.

The authors also noted that each treatment that was assessed in this trial has been linked with clinical benefits across different patient subgroups with colorectal cancer.

“It is well documented that the MAPK pathway is integral in carcinogenesis of mCRC, and that both MEK and WEGF-targeted agents can alter the immune micro-environment and may lead to additive activity when combined with immune checkpoint blockade, providing rationale to study this particular combination,” they wrote in a poster of the findings.

Forty-seven patients (median age, 53.6 years; 53% male) were enrolled into the trial. Enrolled patients were aged at least 18 years old and had disease that progressed after at least two previous lines of treatment.

Patients in the trial were administered 7.5 mg of Avastin intravenously every three weeks, 200 mg of Keytruda intravenously every three weeks and 45 mg of Mektovi orally twice a day until disease progressed or patients experienced unacceptable toxicities.

Assessing response rates to the triplet regimen was the main goal of the study. Other goals included measuring progression-free survival, objective response rate (the percentage of patients with partial and complete responses to the treatment), disease control rate at two months (which was time of first re-staging), duration of response, overall survival, safety and tolerability.

The findings showed that five patients achieved a partial response, 24 patients reached stable disease and 29 patients derived a clinical benefit at the first re-staging at 2 months. The analysis also demonstrated that the triplet induced a median progression-free survival of 5.8 months.

In terms of Mektovi dose reductions, 14 patients had to be switched to 30 mg twice per day, 12 were reduced to 15 mg twice per day and one patient discontinued treatment. The most common less serious or severe side effects included, but were not limited to, 34 cases of rash, 24 cases of diarrhea and 18 cases of nausea.

“Toxicity from these three approved drugs is well-established and observed toxicity in this trial was as expected,” the authors concluded. “The combination … has promising activity in treatment-refractory mCRC with some patients achieving deep and durable responses and a majority of patients deriving clinical benefit at time of first disease re-staging.”

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