ASCO Conference Coverage

Study: First-Line ICI Plus Chemotherapy, Anlotinib Improves Progression-Free Survival in Advanced Endometrial Cancer

Anthony Calabro, MA

Key Highlights

  • Benmelstobart + chemotherapy + anlotinib improved objective response rate and significantly prolonged progression free survival versus benmelstobart + chemotherapy alone.
  • Progression-free survival benefit was notable in the mismatch repair–proficient subgroup.
  • Grade ≥ 3 adverse events were common but comparable between treatment arms.

The addition of the anti-angiogenic agent anlotinib to benmelstobart (BMSB) and standard chemotherapy improved clinical outcomes in patients with advanced or recurrent endometrial cancer in a phase II randomized trial presented at the American Society of Clinical Oncology 2025 annual meeting in Chicago, IL.

Objective response rate (ORR) was higher in the combination arm (86.1%) compared with BMSB and chemotherapy alone (80.6%). Additionally, a statistically significant progression-free survival (PFS) benefit was observed with the addition of anlotinib (ALTN), particularly in patients with mismatch repair-proficient (pMMR) tumors—a group traditionally less responsive to immunotherapy.

Although there is an established role for immune checkpoint inhibitors like BMSB in mismatch repair-deficient (dMMR) EC, how to improve efficacy in the more prevalent pMMR subset remains a challenge. The researchers set out to determine whether combining anti-angiogenic therapy with immunotherapy and chemotherapy could modulate the tumor microenvironment and enhance antitumor activity across MMR statuses.

A total of 71 patients with primary advanced stage III/IV or recurrent EC who had not received prior systemic therapy were randomized 1:1. The experimental group received BMSB 1200 mg plus carboplatin/paclitaxel and ALTN during induction, followed by BMSB and ALTN maintenance. The control arm received BMSB and chemotherapy, followed by BMSB maintenance. Treatment was stratified by MMR status. At data cutoff (November 1, 2024), the median follow-up was 16.2 months for the combination group and 14.2 months for the control arm.

Patients in the BMSB + ALTN group experienced a PFS benefit (hazard ratio [HR], 0.38; 95% CI, 0.18-0.81), with median PFS not reached versus 8.41 months in the BMSB group. Among patients with pMMR tumors, the PFS advantage remained significant (HR, 0.35; 95% CI, 0.15-0.79). Median overall survival was not reached in either arm (HR, 0.29; 95% CI, 0.07-1.16). The safety profile was similar across arms, with Grade ≥ 3 treatment-emergent adverse events occurring in 81.6% of the BMSB + ALTN group and 75.8% of the BMSB group. Common high-grade toxicities included neutropenia, thrombocytopenia, and anemia.

Despite the relatively small sample size and immature overall survival data, these findings suggest that the triplet regimen may represent a valuable first-line option for advanced EC, especially in patients with pMMR tumors, according to the study authors.

“Benmelstobart combined with carboplatin/paclitaxel and anlotinib, followed by maintenance benmelstobart and anlotinib, demonstrated clinically meaningful ORR and PFS benefits in patients with previously untreated advanced or recurrent EC,” the authors concluded. “The regimen was particularly helpful in improving outcomes for patients with pMMR tumors, potentially providing a new treatment option.”

Reference
Chen X, Zhang K, Wang K, et al. Benmelstobart plus carboplatin/paclitaxel with or without anlotinib, followed by maintenance benmelstobart with or without anlotinib, as first-line treatment for advanced or recurrent endometrial cancer: A randomized, open-label, phase II trial. Presented at: 2025 American Society of Clinical Oncology Annual Meeting; 2025 May 30–June 3; Chicago, IL.