A meta-analysis of induction chemotherapy (ICT) followed by chemoradiotherapy for locally advanced cervical cancer: The role of ICT type and duration on efficacy outcomes.

Abstract

5539 Background: The treatment of locally advanced cervical cancer (LACC) is based on concomitant chemotherapy and radiotherapy (CCRT). While the recent incorporation of pembrolizumab for stage III-IVA disease has expanded treatment options, immunotherapy remains inaccessible in many regions with high cervical cancer prevalence. The addition of induction chemotherapy (ICT) prior to CCRT is controversial, as trials have yielded conflicting results. This study aims to evaluate the impact of the type and duration of the ICT for LACC. Methods: We systematically searched PubMed, Embase and Cochrane for studies with patients diagnosed with LACC receiving ICT followed by CCRT. Studies that included surgery, definitive radiotherapy (without concurrent chemotherapy), or immunotherapy were excluded. We compared ICT regimens between each other based on drug type and duration, and conducted a meta-analysis of trials comparing ICT followed by CRT versus CRT alone. Meta-analyses were carried out using random-effects model, with heterogeneity assessed via I² statistics and Cochran’s Q test. Sensitivity analyses were performed using the leave-one-out approach, and meta-analyses of proportions with subgroup analyses. Results: Among 5,282 screened studies, 20 met the inclusion criteria, representing 1,543 patients treated with ICT. Meta-analysis of proportions revealed a 2-year overall survival (OS) of 84.1% for studies utilizing platinum–paclitaxel compared to 72.2% for platinum–gemcitabine (p-value for subgroup difference = 0.022). Studies with ICT duration of ≤6 weeks showed a 2-year OS of 84.8% compared to 71.7% for ICT duration >6 weeks (p = 0.003). Other subgroup comparisons (cisplatin versus carboplatin, cycle duration of ≤14 days versus >14 days, and cisplatin dose intensity <25 mg/m²/week versus ≥25 mg/m²/week) did not show statistically significant differences in 2-year OS. A meta-analysis of the five controlled studies exhibited high heterogeneity in OS and progression-free survival (PFS), driven by the CIRCE trial — the only study employing a platinum–gemcitabine ICT regimen lasting >6 weeks. Sensitivity analysis excluding this trial demonstrated a significant improvement in OS (HR 0.68; 95% CI 0.47–0.99; p = 0.049) and PFS (HR 0.46; 95% CI 0.31–0.69; p = 0.0002) with the addition of ICT to CCRT, compared to CCRT alone. Conclusions: In patients with LACC, the addition of ICT to CCRT significantly improves PFS and OS compared to CCRT alone, provided that the ICT involves a platinum doublet with paclitaxel and is administered within ≤6 weeks.