Lenvima Plus Keytruda Bests Chemotherapy for Advanced Endometrial Cancer

The two-drug combination of Lenvima (lenvatinib) plus Keytruda (pembrolizumab) improved survival outcomes for patients with pretreated advanced endometrial cancer, compared with chemotherapy, according to findings from the Study 309/KEYNOTE-775 clinical trial.

The drug duo improved progression-free survival (time from treatment until disease worsens), overall survival (time from treatment until death from any cause) and overall response rate (percentage of patients whose disease shrinks from treatment) regardless of the patients’ mismatch repair (MMR) status.

MMR status describes cellular genetic mutations that cause mistakes to happen when DNA is copied in a cell. The DNA mutations that result from MMR deficiency (dMMR) can result in cancer, while the absence of these mutations is called proficient MMR (pMMR).

The trial included 827 patients: 697 with proficient MMR (pMMR) and 130 with deficient MMR (dMMR). To be eligible, patients must have experienced disease progression after a prior systemic, platinum-based chemotherapy regimen and have an Eastern Cooperative Oncology Group performance status of 0 or 1, meaning that their disease has little, if any, effect on the performance of their daily activities.

Patients on the trial were randomly assigned to receive Lenvima plus Keytruda or physicians’ choice of chemotherapy (either doxorubicin or paclitaxel).

“Consistent with the interim analysis results, at the final pre-specified overall survival analysis, (Lenvima) plus (Keytruda) continued to demonstrate clinically meaningful improvements in overall survival, progression-free survival and overall response rate versus chemotherapy in pMMR and all-comer patients with advanced endometrial cancer who received prior platinum therapy, supporting the robustness of the treatment effect that was observed at the interim analysis,” study author Dr. Vicky Makker, an associate attending physician at Memorial Sloan Kettering Cancer Center in New York City, said in a presentation of the data at the 2022 European Society for Medical Oncology Congress.

In the overall study population, average progression-free survival was better in the Lenvima/Keytruda group at 7.3 months compared to the chemotherapy group, at 3.8 months. Progression-free survival was also better in the pMMR subgroup who received the drug duo (6.7 months) versus chemotherapy (3.8 months).

Patients receiving the Lenvima/Keytruda regimen tended to live longer, too. Overall survival was 18.7 months in the investigational group compared to 11.9 months in the chemotherapy group. For patients who had pMMR disease, the average overall survival was 18 months in the Lenvima/Keytruda group and 12.2 months in the chemotherapy group.

Of note, 10% of patients with pMMR disease and 8.7% of the entire study population who were assigned to receive chemotherapy ended up receiving subsequent treatment with Lenvima plus Keytruda.

Patients in the Lenvima/Keytruda group had a median overall response rate of 33.8 months compared with 14.7 months in the chemotherapy group. For those with pMMR advanced endometrial cancer, average overall response rate was 32.4 months and 15.1 months in the investigational and physicians’ choice groups, respectively.

“Treatment-emergent (side effects) were also consistent with the primary analysis,” Makker said.

Serious side effects occurred in 79% of patients receiving Lenvima plus Keytruda, compared to 60% of patients in the chemotherapy group. The most common serious side effects for those in the Lenvima/Keytruda group were hypertension (39%), weight loss (11%) and diarrhea and decreased appetite, which each occurred in less than 10% of patients.

Seventy-two percent of patients receiving the Lenvima/Keytruda combination had a treatment interruption. Sixty-seven percent of patients had a dose reduction for Lenvima, with the drug being discontinued in 36% of patients. Twenty-two percent of patients discontinued treatment with Keytruda, and 16% of patients discontinued both drugs.

“These results continue to support the use of (Lenvima) plus (Keytruda) as a standard therapy in patients with previously treated advanced endometrial cancer,” Makker concluded.

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