Efficacy of Endostar plus concurrent chemoradiotherapy in locally advanced cervical cancer: a multicenter, phase II randomized trial.

Abstract

Background: Cervical cancer remains the fourth most common malignant cancer in females and the fourth most common cause of mortality in women worldwide. Approximately 70% of new cases are diagnosed as locoregionally advanced cervical cancer (LACC), posing a significant threat to women's health. Concurrent chemoradiotherapy (CCRT) is the established standard treatment for LACC. However, more than 30% of patients still experience local recurrence and distant metastasis. Improving treatment outcomes for LACC is a critical global objective.

Objective: To investigate the safety and efficacy of adding Endostar to CCRT in patients with LACC.

Design: This is a multicenter, open-label, randomized, controlled, phase II trial.

Methods: A total of 120 patients were randomly allocated (1:1) to receive either CCRT alone (definitive radiotherapy plus cisplatin 40 mg/m² every week for 4-5 cycles) or CCRT plus Endostar, Endostar at a dose of 7.5 mg/m²/day, from 5 days before CCRT for 10 consecutive days every 15 days for four cycles).

Results: The CCRT + E arm demonstrated a significantly higher complete response rate (CRR) compared to the CCRT arm (68.3% vs 35.0%, p = 0.001), while the overall response rate (ORR) was similarly in both arms (98.3% vs 100%, p = 1.000). The CCRT + E arm showed significantly improved distant metastasis-free survival (DMFS) (1-year: 91.6% vs 94.8%, 2-year: 82.3% vs 91.6%, 5-year: 67.0% vs 88.0% p = 0.029). No significant differences were found in overall survival (OS), progression-free survival (PFS), or locoregional recurrence-free survival (LRFS) (p > 0.05). Multivariable analysis identified maximum tumor diameter >4 cm and failure to achieve CR as predictive factors of poor PFS, and maximum tumor diameter >4 cm and stage IIIA-IVA disease as poor prognostic factors for OS. According to the subgroup analysis, Endostar significantly improved the DMFS in cohorts of patients with squamous cell carcinoma (p = 0.005), a maximum tumor diameter > 4 cm (p = 0.011), and stage IB2 or IIA2-IIB disease (p = 0.005). The rates of acute and late adverse reactions were similar in both arms (p > 0.05), with no cardiac toxicity, hypertension, or grade 5 toxicity reported.

Conclusion: The addition of Endostar to CCRT significantly enhanced tumor response (CRR) and reduced distant metastasis (DMFS) in LACC patients without increasing treatment toxicity, offering a promising therapeutic enhancement. Clinically, patients with squamous cell carcinoma, maximum tumor diameter > 4 cm, and International Federation of Gynecology and Obstetrics stage IB2 or IIA2-IIB disease derived particularly robust DMFS benefits from the combination regimen, suggesting they should be prioritized for this approach. Although the 5-year DMFS results are encouraging, validation in a larger phase III study and longer follow-up are warranted before considering this regimen as a new standard treatment modality for LACC.

Trial registration: This trial was registered at ClinicalTrials.gov (NCT03086681, registered 22 March 2017, https://clinicaltrials.gov/study/NCT03086681.