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Treatment with sintilimab (Tyvyt) plus anlotinib demonstrated a potential long-term survival benefit in patients with PD-L1–positive, recurrent or metastatic cervical cancer, according to updated findings from a phase 2 trial (ChiCTR1900023015) published in BioMed Central Medicine.
Findings showed that at a median follow-up of 47.2 months (range, 0.6–52.9) at the July 12, 2024, data cutoff, the regimen (n = 42) produced a median overall survival (OS) of 17.8 months (95% CI, 12.3-36.5). The respective 1-, 2-, and 3-year OS rates were 69.2% (95% CI, 53.4%-83.2%), 43.6% (95% CI, 30.5%-62.3%), and 33.3% (95% CI, 21.4%-51.9%).
“Our study suggests that sintilimab plus anlotinib exhibits durable antitumor activity and long-term survival benefit in patients with pretreated PD-L1–positive advanced cervical cancer, which might be an alternative treatment option. For patients experiencing progression after sintilimab plus anlotinib, chemotherapy may still be the essential treatment option,” lead study author Jing Liu, MD, of the Department of Gynecology at the Clinical Oncology School of Fujian Medical University in China, and colleagues wrote in a publication of the data.
Phase 2 Study Design
This multicenter, single-arm phase 2 trial enrolled patients 18 to 75 years of age with pathologically confirmed recurrent or metastatic cervical cancer who had a PD-L1 combined positive score of at least 1. Eligible patients had experienced disease progression following at least 1 prior systemic therapy or were unable to tolerate chemotherapy. Patients also needed to have an ECOG performance status of 0 or 1.
All enrolled patients received intravenous sintilimab at 200 mg on day 1 plus oral anlotinib at 10 mg on days 1 through 14 of each 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, death, withdrawal of consent, or initiation of alternative antitumor therapy. Patients who discontinued study treatment due to progression could receive subsequent therapy at the investigator’s discretion.
The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), OS, and disease control rate.
Additional Efficacy Findings, Including Data Following Progression
Responders (n = 23) achieved a median duration of response (DOR) of 13.2 months (95% CI, 8.2-41.8).
Among the 42 patients enrolled, 13 received subsequent treatment following progression on sintilimab plus anlotinib; the remaining 29 patients did not receive subsequent therapy due to poor performance status, financial constraints, personal decision, or death.
Among the 13 patients who did receive additional therapy, 10 were evaluable for response.
Two of these 10 patients achieved complete response (CR) to subsequent therapy, four achieved partial response (PR), and two had stable disease, yielding an second ORR (ORR2) of 46.1% (95% CI, 23.1%-71.8%) and a second disease control rate (DCR2) of 61.5% (95% CI, 31.6%-86.1%) in the 13-patient subgroup. Among the 10 evaluable patients, the ORR2 was 60.0% (95% CI, 26.6%-87.1%) and DCR2 was 80.0% (95% CI, 44.3%-97.2%). Median time to second PFS (PFS2) was 23.6 months (95% CI, 12.5-29.8), with a median interval of 7.5 months (95% CI, 5.8-not reached [NR]) from first to second disease progression.
In terms of subsequent therapy received by the 13 patients, 8 patients (61.5%) received platinum-based chemotherapy alone or part of a combination. These patients had a median platinum-free interval of 5.5 months (range, 1.4-56.1) prior to starting sintilimab plus anlotinib and 19.0 months (range, 9.2-69.0) before initiating subsequent therapy. Two achieved CR and two achieved PR, translating to an ORR2 of 50.0%. Three patients who received platinum-based chemotherapy as subsequent treatment remained alive and progression-free at the data cutoff, with a median PFS2 of 23.1 months (95% CI, 13.9-NR).
Five patients received non–platinum-based regimens as subsequent treatment, with two achieving PR (ORR2, 40.0%); all had disease progression by data cutoff. Albumin-bound paclitaxel was administered to 6 patients (46.2%), resulting in two CRs and two PRs (ORR2, 66.7%); 3 remained alive and progression-free. In contrast, among the 7 patients who did not receive albumin-bound paclitaxel, only 2 achieved PR (ORR2, 28.6%), and all had experienced disease progression by data cutoff.
Immune checkpoint inhibitors (ICIs) were included in the treatment regimen for 6 patients (46.2%), with four achieving PR (ORR2, 66.7%) and 1 maintaining a sustained response without disease progression. Among the seven patients who did not receive ICI, two achieved CR (ORR2, 28.6%), with 2 patients alive and progression-free at the time of the analysis.
Safety Profile
Sintilimab plus anlotinib demonstrated a manageable safety profile, with most adverse effects (AEs) being grade 1 or 2 in severity. The most common any-grade AE was hypothyroidism, occurring in 33.3% of patients, with all instances being grade 2. Other frequently reported AEs included increased aspartate aminotransferase levels (21.4%), hypertension (19.0%), palmar-plantar erythrodysesthesia (19.0%), diarrhea (16.7%), increased alanine aminotransferase levels (16.7%), and fistula formation (14.3%).
Grade 3 hypertension and diarrhea were each reported in 2.4% of patients, while fistula occurred at grade 3 in 7.1%. Any-grade immune-related AEs included hypothyroidism (33.3%), immune pneumonitis (4.8%; 1 grade 3 case), and immune myocarditis (2.4%; 1 grade 3 case). Laboratory abnormalities such as hypertriglyceridemia (14.3%), anemia (11.9%), and hypercholesterolemia (11.9%) were observed but were primarily low-grade.
Reference
Liu J, Lan C, Liu T, et al. Long-term efficacy and updated survival outcomes of sintilimab plus anlotinib in patients with PD-L1-positive recurrent or metastatic cervical cancer. BMC Medicine. 2025;23(1). doi:10.1186/s12916-025-04198-5