Israt Jahan Riya

Efficacy and safety of immune checkpoint inhibitors with chemoradiotherapy/chemotherapy in locally advanced cervical cancer patients: a systematic review and single-arm meta-analysis

Recent advancements highlight promising outcomes with immune checkpoint inhibitors (ICIs) when combined with concurrent chemoradiotherapy (CCRT) or chemotherapy in the treatment of locally advanced cervical cancer (LACC). This systematic review and meta-analysis aimed to assess the efficacy and safety of ICIs combined with CCRT/chemotherapy in patients with LACC. We searched PubMed, Embase, Cochrane and ClinicalTrials.gov for randomized controlled trials (RCTs) and non-RCTs assessing the efficacy and safety of ICIs plus CCRT/chemotherapy in patients with LACC. All analyses were performed in R software (v.4.4.0). Our systematic review and meta-analysis included 3 RCTs and 4 observational studies, corresponding to 1,250 patients. The 1-year progression-free survival (PFS) was 78% (95% confidence interval [CI]=75-80, I²=0%), while the 1-year overall survival (OS) reached 93% (95% CI=89-95, I²=50%). The objective response rates were 88% (95% CI=74-95, I²=74%). We performed a comparative analysis of PFS and OS using data from the 2 RCTs. The results indicated that the ICI plus CCRT group had a significantly lower risk of disease progression or death compared to the CCRT group alone (PFS: hazard ratio [HR]=0.76, 95% CI=0.64-0.91, I²=4%; OS: HR=0.76, 95% CI=0.58-0.98, I²=0%), representing an approximate 25% reduction in risk. The analysis of grade ≥3 adverse events revealed the low incidences, with none exceeding 15%. Our findings suggest that ICIs are effective and safe to use with CCRT/chemotherapy in LACC patients. Further RCTs are needed to confirm these findings. International Prospective Register of Systematic Reviews Identifier: CRD42024576145.

Adjuvant, neoadjuvant, and surgical treatment for locally advanced cervical cancer: a Bayesian network meta-analysis

Concurrent chemoradiotherapy remains the standard of care for locally advanced cervical cancer. Alternative strategies, such as induction chemotherapy followed by concurrent chemoradiotherapy and the addition of immune checkpoint inhibitors, show promise but lack consensus. Other approaches, including adjuvant chemotherapy and surgery, have also been explored. This network meta-analysis compared the efficacy of these approaches. A systematic review identified randomized controlled trials evaluating treatments for International Federation of Gynecology and Obstetrics stage IB2 to IVA locally advanced cervical cancer. Interventions included concurrent chemoradiotherapy, induction chemotherapy, neoadjuvant or adjuvant chemotherapy, radiotherapy alone, concurrent chemoradiotherapy with immune checkpoint inhibitors, surgery, or their combinations. Progression-free and overall survival were assessed. HRs were extracted or reconstructed using individual patient data from Kaplan-Meier curves. A Bayesian network meta-analysis with random-effects models was conducted, with treatment rankings based on surface under the cumulative ranking curve and superiority probabilities. Forty-seven trials (14,155 patients; 89% with squamous histology) were included. For overall survival (41 trials, 12,241 patients), no significant differences were observed among treatments, but concurrent chemoradiotherapy showed a trend toward superiority over radiotherapy alone (HR 0.84, 95% credible interval; 0.67-1.06; superiority probability = 93.1%). For progression-free survival (39 trials, 11,825 patients), concurrent chemoradiotherapy outperformed radiotherapy and induction chemotherapy followed by radiotherapy but showed similar efficacy to immune checkpoint inhibitor combinations, adjuvant chemotherapy, or induction chemotherapy. Concurrent chemoradiotherapy with immune checkpoint inhibitors ranked highest for both outcomes. Concurrent chemoradiotherapy remains more effective than radiotherapy alone or surgery and comparable to other combination strategies. These findings support it as the cornerstone of treatment for locally advanced cervical cancer while highlighting the promise of immune checkpoint inhibitor-based approaches.