Lenvatinib plus pembrolizumab in participants with advanced or recurrent endometrial cancer: Study 309/KEYNOTE-775 and ENGOT-en9/LEAP-001 post-(neo)adjuvant therapy outcomes

Objective: We report outcomes for the sub-group of participants who only received neoadjuvant, adjuvant, or neoadjuvant+adjuvant platinum-based chemotherapy before enrollment in the phase 3 Study 309/KEYNOTE-775 (NCT03517449) and ENGOT-en9/LEAP-001 (NCT03884101). Methods: Study 309/KEYNOTE-775 enrolled participants with advanced/recurrent/metastatic endometrial cancer with disease progression after 1 previous line of platinum-based chemotherapy (2 allowed if initially given as [neo]adjuvant therapy). ENGOT-en9/LEAP-001 enrolled participants with stage III-IV or recurrent, radiographically apparent endometrial cancer and no previous chemotherapy or disease progression ≥6 months after (neo)adjuvant platinum-based chemotherapy. In both trials, participants were randomized 1:1 to lenvatinib 20 mg once daily+pembrolizumab 200 mg every 3 weeks or chemotherapy (doxorubicin or paclitaxel in Study 309/KEYNOTE-775, carboplatin+paclitaxel in ENGOT-en9/LEAP-001). Overall survival and progression-free survival (Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review) were primary endpoints. Results: In Study 309/KEYNOTE-775 (n = 300), median (95% confidence interval) overall survival was 17.4 (14.0 to 22.8) months with lenvatinib+pembrolizumab and 13.3 (10.9 to 15.5) months with chemotherapy (hazard ratio [95% confidence interval], 0.67 [0.52 to 0.87]). Median (95% confidence interval) progression-free survival was 7.2 (5.6 to 8.0) and 3.9 (3.6 to 5.4) months (hazard ratio [95% confidence interval], 0.52 [0.40 to 0.68]). Objective response rates were 34.3% versus 16.6%. In ENGOT-en9/LEAP-001 (n = 121), median (95% confidence interval) overall survival was 35.4 (26.6 to not reached) months with lenvatinib+pembrolizumab and 22.1 (16.4 to 34.8) months with chemotherapy (hazard ratio [95% confidence interval], 0.66 [0.42 to 1.03]). Median (95% confidence interval) progression-free survival was 15.0 (8.3 to 21.0) and 8.3 (6.2 to 10.2) months (hazard ratio [95% confidence interval], 0.52 [0.33 to 0.81]). Objective response rates were 63.5% versus 43.1%. In both trials, the most common treatment-related adverse events with lenvatinib+pembrolizumab were hypertension (62.4%/60.3%) and hypothyroidism (58.2%/60.3%). Conclusions: In this sub-group analysis of participants who only received neoadjuvant, adjuvant, or neoadjuvant+adjuvant platinum-based chemotherapy before enrollment, lenvatinib+pembrolizumab demonstrated better anti-tumor activity and favorable outcomes versus chemotherapy with manageable safety. Lenvatinib+pembrolizumab is approved for patients with advanced endometrial cancer and could be considered an effective treatment option in this sub-group.