KEY TAKEAWAYS
- The phase I and II trials aimed to evaluate the efficacy and safety of F plus S in the cervical cancer cohort.
- The primary endpoint was ORR.
- The results demonstrated that F plus S offered promising efficacy for advanced CC, particularly in PD-L1 CPS ≥1 patients, with manageable side effects.
Fruquintinib (F), a highly selective VEGFR inhibitor, combined with sintilimab (S), an anti-PD-1 monoclonal antibody, demonstrated promising antitumor activity in pre-clinical and clinical studies.
Xiaotian Han and the research group spearheaded a study that aimed to report the outcomes and findings of the combination of F, and S in the cervical cancer (CC) cohort as part of an open-label, multicenter, single-arm phase 2 clinical trial.
Patients with pathologically confirmed advanced CC, who had failed at least first-line platinum-containing treatment, experienced intolerable toxicity, or were unable to receive standard therapy, were eligible. Eligible patients received F at 5 mg (2 weeks on/1 week off, orally, once daily) plus S at 200 mg (IV, every 3 weeks) in 21-day cycles, until disease progression or unacceptable toxicity. Treatment with S was allowed for up to 24 months. The primary endpoint was the objective response rate (ORR) per RECIST v1.1.
About 34 patients were enrolled and treated with F plus S, with a median follow-up of 16.4 months. Median age was 56 years (range: 26.2–73.7). About 6 pts (17.6%) were treatment-naïve (naïve pts), while 82.4% had received at least first-line treatment (treated pts), including bevacizumab (5/28) for advanced disease. Most patients (73.5%) had undergone pelvic radiation therapy, and 70.6% had PD-L1 status CPS ≥1.
In treatment-naïve and treated patients with evaluable tumors, confirmed ORR (cORR) were 50.0% (3/6) and 29.6% (1/27 CR, 7/27 PR), with median time to response of 2.7 and 3.1 months, and 100% disease control rate (DCR) in both groups. Median progression-free survival (mPFS) was 10.3 months for naïve and 8.2 months for treated patients. The 15-month overall survival (OS) rates were 83.3% and 70.0%, respectively.
In treated patients, stratified by PD-L1 CPS ≥1 vs <1 (N=17 vs 8), cORR was 41.2% vs 12.5% (N=18 vs 8),, and mPFS was 19.4 vs 5.2 months, with mOS not reached vs 13.9 months. The 15-month OS rate was 76.0% vs 50.0%.
All patients experienced treatment-emergent adverse events (TEAEs), with common ones including proteinuria (64.7%), hypothyroidism (61.8%), asthenia (44.1%), hyperthyroidism (44.1%), palmar-plantar erythrodysaesthesia syndrome (44.1%), anemia (41.2%), and urinary tract infection (41.2%).
The combination of F and S demonstrated positive efficacy in advanced CC patients, particularly those previously treated with PD-L1 CPS ≥1. Additionally, the treatment exhibited a manageable toxicity profile consistent with other studied cohorts. The research was sponsored by Hutchmed.
Source: https://cslide.ctimeetingtech.com/asia2023/attendee/confcal/show/session/28
Clinical Trial: https://clinicaltrials.gov/study/NCT03903705
Wu X, Wang D, Wang J et al.’’ Fruquintinib plus sintilimab in advanced cervical cancer (CC) patients (pts): Results from a multicenter, single-arm phase II study.’’ Presented at ESMO ASIA 2023 ( Presentation No. 289MO).
