Phase 3 Study Supports Pembrolizumab Plus Lenvatinib as Standard of Care in Patients With Advanced Endometrial Cancer Who Received Prior Platinum Therapy

Data from the phase 3 Study 309/KEYNOTE-775 trial (NCT03517449) showed ongoing clinical benefit in patients with advanced endometrial cancer who received prior platinum therapy and then completed pembrolizumab (Keytruda; Merck & Co) and continued on lenvatinib (Lenvima; Eisai), according to study investigator Emeline Colomba, who presented the results of the trial at the European Society for Medical Oncology (ESMO) 2023 Congress in Madrid, Spain. Colomba explained further that the trial results support lenvatinib plus pembrolizumab as standard of care.

The primary analysis of the study demonstrated that for patients who completed pembrolizumab and continued on lenvatinib, there were clinically and statistically significant improvements in progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared to the chemotherapy arm (all-comers and patients with mismatch repair-proficient [pMMR] tumors). During the trial, patients received pembrolizumab for up to 2 years and then continued treatment with lenvatinib until disease progression or toxicity. In the exploratory analysis of the data, investigators sought to assess outcomes in patients who completed 2 years of pembrolizumab and continued lenvatinib at the final prespecified OS analysis cutoff of March 1, 2022.

During the trial, patients received pembrolizumab for up to 2 years and then continued treatment with lenvatinib until disease progression or toxicity. Image Credit: © Dr_Microbe - stock.adobe.com

Patients with advanced endometrial cancer who received 1 prior platinum-based chemotherapy (up to 2 if 1 was given in the [neo]adjuvant setting) were randomly assigned to receive lenvatinib at 20 mg orally once a day plus pembrolizumab at 200 mg intravenously (IV) every 3 weeks (Q3W) for up to 35 cycles, or chemotherapy (doxorubicin at 60 mg/m2 IV Q3W or paclitaxel 80 mg/m2 IV QW [3 weeks on; 1 week off]). Patients with pMMR tumors were then further stratified by ECOG PS, geographic region, and pelvic irradiation history. Investigators in the trial reported PFS, OS, ORR, duration of response (DOR), and safety in all-comer patients and patients with pMMR tumors who completed 35 cycles (approximately 2 years) of pembrolizumab and then continued lenvatinib.

Of the 411 patients randomly assigned to the lenvatinib plus pembrolizumab arm (pMMR n=346), 41 (pMMR n=30) completed 35 cycles of pembrolizumab and continued on lenvatinib and are included in the analysis. For these patients, median PFS (95% CI) was 34.1 months (20.1-not evaluable [NE]) in patients with pMMR tumors and 34.1 months (27.7-NE) in all-comer patients. Median OS (95% CI) was not reached (NR) in patients with pMMR tumors and all-comer patients. ORR (95% CI) was 63.3% (43.9-80.1) in patients with pMMR tumors and 63.4% (46.9-77.9) in all-comers.

Additionally, 7 patients with pMMR tumors and 8 all-comer patients had a complete response. Further, median DOR was NR (range, 3.5-39.5+) in patients with pMMR tumors and all-comers. For treatment-related adverse events (AEs), grade 3 AEs occurred in 80.5% of all-comer patients.

“Well next steps are investigating further the details of safety in this population,” Colomba said in an interview with Pharmacy Times. “We are not able currently to determine those in this final publication. Then we are waiting to address further the question of this combination in the first-line setting.”

Reference

Colomba E, Lorusso D, Mackay H, et al. 748P - Outcomes for patients (pts) with advanced endometrial cancer (aEC) who completed pembrolizumab (pembro) and continued lenvatinib (LEN) in the phase III Study 309/KEYNOTE-775. ESMO. October 21, 2023. Accessed October 24, 2023. https://oncologypro.esmo.org/meeting-resources/esmo-congress/outcomes-for-patients-pts-with-advanced-endometrial-cancer-aec-who-completed-pembrolizumab-pembro-and-continued-lenvatinib-len-in-the-phase