The National Medical Products Administration (NMPA) of China has granted conditional approval to fruquintinib (Elunate) in combination with sintilimab injection (Tyvyt) for patients with mismatch repair–proficient (pMMR), advanced endometrial cancer who have progressed following prior systemic therapy and are not candidates for curative surgery or radiation. This decision marks a significant advancement in the treatment landscape for this challenging disease.
The approval is based on data from the endometrial cancer registration cohort of the phase 2 FRUSICA-1 study (NCT03903705). This open-label, single-arm trial evaluated the efficacy and safety of the combination therapy in patients with advanced endometrial cancer. The study enrolled patients aged 18 to 75 years with histologically confirmed, inoperable or metastatic advanced endometrial cancer who had progressed on or were intolerant to up to 2 prior lines of systemic platinum-based therapy. Patients were required to have an ECOG performance status of 0 or 1, measurable disease per RECIST v1.1 criteria, and adequate organ function, as well as provide a tumor tissue sample for MMR testing.
Efficacy Data from FRUSICA-1
The FRUSICA-1 study demonstrated promising results for the combination of fruquintinib and sintilimab. Among the 87 patients in the study, the objective response rate (ORR) was 35.6% (95% CI, 25.6%-46.6%) as assessed by an independent review committee (IRC). This included a complete response rate of 2.3% and a partial response rate of 33.3%. The disease control rate (DCR) was 88.5% (95% CI, 79.9%-94.3%). The duration of response (DOR) rate at 9 months was 80.7% (95% CI, 56.3%-92.3%), and the median time to response (TTR) was 1.6 months (95% CI, 1.4-2.8).
At a median follow-up of 7.9 months, the median progression-free survival (PFS) was 9.5 months by RECIST v1.1 criteria and IRC assessment, with a 6-month PFS rate of 59.5% (95% CI, 48.1%-69.2%). Notably, the median PFS was 13.8 months in patients who had previously received bevacizumab (Avastin; n = 22) and 9.5 months in those who had not (n = 76). The median overall survival (OS) was 21.3 months, and the 12-month OS rate was 69.4% (95% CI, 58.2%-78.2%). In patients with or without prior bevacizumab history, the median OS was not reached and 21.0 months, respectively.
Dosing and Treatment Schedule
In the FRUSICA-1 trial, participants received oral fruquintinib at 5 mg once daily on a 2-week-on/1-week-off schedule, combined with intravenous sintilimab at 200 mg every 3 weeks as part of 3-week cycles. Treatment continued until disease progression or unacceptable toxicity, with sintilimab treatment capped at 24 months. The primary endpoint of the study was ORR per RECIST criteria and IRC assessment, while key secondary endpoints included DCR, DOR, TTR, PFS, and OS.
Safety Profile
The median duration of treatment exposure was 6.01 months (range, 0.7-35.9). Almost all patients (98%) experienced any treatment-related adverse effect (TRAE), with 60.2% experiencing grade 3 or higher effects. Serious TRAEs were reported in 20.4% of patients. TRAEs led to dose reduction of fruquintinib in 40.8% of patients, interruption of any drug in 52.0% of patients, and discontinuation of any drug in 13.3% of patients.
The most common TRAEs (≥30% of patients) were hypothyroidism (52%), proteinuria (43.9%), hypertension (43.9%), palmar-plantar erythrodysesthesia (38.8%), increased aspartate aminotransferase level (33.7%), and asthenia (30.6%). Most TRAEs were grade 1 or 2, except for hypertension, palmar-plantar erythrodysesthesia syndrome, and hypertriglyceridemia.
Clinical Implications
According to Dr. Xiaohua Wu, Director of the Department of Gynecologic Oncology at Fudan University Affiliated Cancer Hospital and principal investigator of the FRUSICA-1 study, this approval could represent a paradigm shift in managing this challenging disease, leveraging the synergistic effects of targeted therapy and immunotherapy to address a critical gap in treatments for patients with limited responses to traditional therapies. The availability of this treatment option brings hope for improved survival and enhanced quality of life for patients with advanced endometrial cancer.
