Efficacy and safety of adjuvant chemotherapy for locally advanced cervical carcinoma: An updated systematic review and meta-analysis of individual patient data and aggregate data.

Abstract

e17518 Background: Cervical cancer is the fourth most common cancer among women globally. Adjuvant chemotherapy (ACT) is added to concurrent chemo-radiotherapy (CCRT) for the treatment of locally advanced cervical cancer (LACC) to reduce recurrence and mortality rates by targeting residual malignant cells. Several studies have emerged since the previous meta-analysis conducted in 2023. We have conducted the largest and updated meta-analysis to assess the latest clinical efficacy of adjuvant chemotherapy Methods: A comprehensive literature search was conducted on MEDLINE, Embase, and Google Scholar up to September 2024. We included randomized controlled trials (RCTs) and observational studies reporting hazard ratios (HRs) and risk ratios (RRs) with corresponding 95% confidence intervals (CIs). The Higgins I 2 index was used for the assessment of heterogeneity. The results of individual studies were pooled by random-effects models on R version 4.4.3 using the “meta” package. Individual Patient Data were generated from Kaplan Meier curves using the “IPDfromKM” package for studies not reporting HR . This review was registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42024543083 Results: A total of 25 studies with 7845 patients were included. ACT was associated with significant improvement in overall survival (HR = 0.70; 95% CI = 0.52 - 0.93; p-value = 0.01; I 2 = 58%), progression-free survival (HR = 0.79; 0.66 - 0.94; p-value = 0.01; I 2 = 48%), and disease metastasis rate (RR = 0.67; 95% CI = 0.47 - 0.96; p-value = 0.01; I 2 = 59%) compared to CCRT alone. However, none of the groups were significantly associated with improved disease-free survival (RR = 1.10; 95% CI = 0.92 - 1.31; p-value < 0.01; I 2 = 73%). Subgroup analyses indicated that ACT was not linked with improved PFS and OS in randomized trials and studies with larger sample sizes (n > 100). Moreover, ACT was associated with a greater rate of hematologic (anemia, neutropenia, thrombocytopenia, leukopenia) and non-hematological toxicities such as vomiting and diarrhea (p-value < 0.05). Conclusions: ACT shows a significant improvement in overall survival and progression-free survival in LACC patients. However, our study results are greatly influenced by heterogeneity and differences in methodology among the pooled studies. Due to significant association with both hematological and non-hematological toxicities, it remains inconclusive whether patients can truly benefit from ACT. More studies are warranted to establish the survival benefits of ACT in LACC patients.