The impact of prior neoadjuvant/adjuvant chemotherapy (NACT/ACT) on fruquintinib plus sintilimab outcomes in advanced endometrial cancer (EMC) patients with pMMR status: A subgroup analysis of FRUSICA-1.

5611 Background: FRUSICA-1 (NCT03903705) was an open-label, single-arm, pivotal phase 2 study to evaluate the efficacy and safety of fruquintinib (F, a highly selective VEGFR inhibitor) plus sintilimab (S, an anti-PD-1 monoclonal antibody) in previously treated advanced EMC patients (pts) with pMMR (proficient mismatch repair) status. The primary results of FRUSICA-1 have demonstrated encouraging efficacy (objective response rate [ORR]: 35.6%; median progression-free survival [PFS]: 9.5 mo; median overall survival [OS]: 21.3 mo) in the overall population (Wu X, et al; 2024 ASCO). In this updated exploratory analysis (data cutoff: May 15, 2024), we evaluated the association between prior NACT/ACT and clinical outcomes in this study. Methods: Pts who had histologically confirmed advanced EMC with pMMR status confirmed by central lab and had progression on 1 standard systemic therapy were eligible. They received F (5 mg QD, 2 weeks on/1 week off, orally) plus S (200 mg, IV, Q3W) in 21-day cycles until disease progression or unacceptable toxicity. The efficacy subgroup analysis was performed by prior NACT/ACT (Yes vs No). Results: As of May 15, 2024, a total of 98 EMC pts with pMMR status were enrolled and received the treatment with the median follow-up of 22.0 mo (95%CI: 20.5, 23.7). Based on pts with or without prior NACT/ACT (Yes vs No = 47 pts vs 51 pts), the baseline demographics and disease characteristics were well balanced. Independent Review Committee (IRC)-assessed ORR (34.0% vs 31.4%) and disease control rate (DCR, 85.1% vs 82.4%) were comparable, respectively. Median duration of response (DoR) in pts with NACT/ACT was 11.1 mo while not reached for pts without NACT/ACT. Median PFS were 7.1 mo (95%CI: 4.7, 13.8) vs 9.5 mo (95%CI: 5.5, not estimable), respectively with two 95%CIs highly overlapped. The 6-mo PFS rates were also comparable at 56.8% vs 59.7%. Median OS pending maturity, the 18-mo OS rates were nearly identical (58.7% vs 59.1%). Conclusions: In this updated exploratory analysis of pts with advanced EMC enrolled in FRUSICA-1 study treated with F plus S, encouraging outcomes were achieved in the overall population, including patients who had received prior NACT/ACT and those who had not, with durable and clinically meaningful responses. Clinical trial information: NCT03903705 .