AACR 2022: Olaparib in combination with cyclophosphamide and metformin performs well in endometrial cancer (ENDOLA trial)

Endometrial cancer occurs primarily in postmenopausal women between the ages of 50 and 60 and is one of the most common gynecological cancers, ranking fourth in incidence of cancer among women and eighth in age-adjusted mortality

The therapeutic effect of endometrial cancer depends on its histological features, disease grade and stage

At the 2022 AACR Annual Meeting, data from the ENDOLA trial (NCT02755844) showed that olaparib in combination with cyclophosphamide and metformin demonstrated favorable disease progression-free rates in patients with recurrent advanced or metastatic endometrial cancer

ENDOLA is a phase 1/2 open-label, dose-escalation trial evaluating olaparib in combination with cyclophosphamide and metformin metronomic therapy in elderly patients with multiple prior therapy for recurrent advanced endometrial cancer

During the dose escalation phase of ENDOLA, olaparib was started at 150 mg twice daily in Cycle 1 and escalated to 300 mg twice daily

In the phase 1 study, dose-limiting toxicities occurred in 5.

Notably, the median age was 69 years (46-80 years), and more than half of the patient population had received at least 4 lines of prior therapy (4-5 lines, 25.

In the Phase 2 portion of the trial evaluating this dose, the 10-week progression-free rate in 14 evaluable patients was 61.

In addition to determining the recommended dose for the Phase 2 trial of the triplet, other primary endpoints in the Phase 1 portion of the study were safety, dose-limiting toxicity and treatment-related adverse reactions (TRAEs)

TRAEs were observed in more than 10% of evaluable patients

Twelve patients (38%) had dose reductions, nine of whom had at least two reductions

In the phase 2 portion, investigators assessed progression-free rates at 10 weeks

A notable secondary endpoint of the Phase 2 portion was progression-free survival (PFS)

The investigators further compared the PFS data with data from the KEYNOTE-755 trial (NCT03517499) in which patients with advanced endometrial cancer who had received at least 1 prior platinum-based chemotherapy regimen received 20 mg of lenvatinib (Lenvima) Oral once daily plus pembrolizumab (Keytruda) 200 mg intravenously every 3 weeks (n=411), or chemotherapy of physician's choice (n=416)