Fruquintinib-Sintilimab Combination Achieves 32.7% Response Rate in Advanced pMMR Endometrial Cancer
核心洞察
A multicenter Phase Ib/II trial demonstrated that the combination of fruquintinib and sintilimab achieved a 32.7% objective response rate in 98 patients with advanced mismatch-repair proficient endometrial cancer (搜索).
The median progression-free survival reached 8.6 months for the total population, with hypertension (搜索) being the most common grade ≥3 treatment-related adverse event at 17.3%.
This combination therapy offers a promising treatment option for patients with previously treated advanced pMMR endometrial cancer (搜索) who had limited therapeutic alternatives.
A novel combination therapy pairing fruquintinib with sintilimab has demonstrated promising efficacy in patients with advanced mismatch-repair proficient (pMMR) endometrial cancer (搜索), according to results from the FRUSICA-1 Phase Ib/II trial published in Nature Communications. The study enrolled 98 Chinese patients with inoperable or advanced pMMR endometrial cancer who had progressed on or could not tolerate up to two prior platinum-based therapies.
Trial Design and Patient Population
The FRUSICA-1 study (ClinicalTrials.gov identifier NCT03903705) was conducted as a multicenter, single-arm trial comprising both exploratory and pivotal phases. Patients received fruquintinib at 5 mg orally once daily on a 2 weeks on/1 week off schedule, combined with sintilimab at 200 mg intravenously once every 3 weeks. The primary endpoint was objective response rate (ORR) as assessed by an independent review committee (IRC).
Efficacy Results
By May 15, 2024, the IRC-assessed ORR reached 32.7% (95% confidence interval [CI] 23.5–42.9) for the total pMMR population of 98 patients. For the pivotal population of 76 patients, the ORR was 31.6% (95% CI 21.4–43.3). The median progression-free survival was 8.6 months (95% CI 5.5–16.6) for the total population and 7.1 months (95% CI 5.4–16.6) for the pivotal population.
Safety Profile
The combination therapy demonstrated a tolerable safety profile. The most common grade ≥3 treatment-related adverse event was hypertension (搜索), occurring in 17.3% of patients. Secondary endpoints included disease control rate, time to response, duration of response, tumor shrinkage, overall survival, and comprehensive safety assessments.
Mechanism of Action
Fruquintinib functions as a vascular endothelial growth factor receptor (搜索) inhibitor, targeting tumor angiogenesis by inhibiting blood vessel growth. Sintilimab operates as an immune checkpoint inhibitor, working to enhance immune system activity against cancer cells. The combination aims to create a synergistic effect that improves patient outcomes in this challenging patient population.
Clinical Significance
The study addresses a significant unmet medical need for patients with pMMR advanced endometrial cancer (搜索), who previously had limited therapeutic alternatives. The researchers concluded that fruquintinib plus sintilimab showed promising efficacy and tolerable safety in previously treated, advanced pMMR endometrial cancer, representing a potential advancement in treatment options for this patient population.