Beyond Platinum, ICIs in Metastatic Cervical Cancer: A Systematic Review

SIMPLE SUMMARY: Approaches beyond first-line chemotherapy to treat advanced cervical cancer (CC) are currently limited. Immune checkpoint inhibitors (ICIs) are showing high efficacy, thus remodeling the therapeutic scenario of many solid tumors. With our systematic review, we aimed to summarize the latest clinical trials using ICIs in CC. Our systematic review managed to demonstrate that ICIs might represent an appealing strategy for advanced CC, with 2 out of 3 patients responding to ICIs without further concerns about safety. PD-L1 status might be an indicator of response; however, the search for new predictive biomarkers is mandatory. Further studies are needed for appropriate patient selection and a tailored approach. ABSTRACT: Background: Cervical cancer (CC) constitutes the fourth most common tumor among the female population. Therapeutic approaches to advanced CC are limited, with dismal results in terms of survival, mainly after progression to platinum-based regimens. Immune checkpoint inhibitors (ICIs) are remodeling the therapeutic scenario of many solid tumors. The role of ICIs in CC should be addressed. Therefore, we systematically reviewed the latest clinical trials employing ICIs in advanced CC to assess which ICIs have been employed and how ICIs might meet the need for new therapeutic options in terms of efficacy and safety. Methods: The review was conducted following the PRISMA guidelines. The following efficacy outcomes were specifically collected: overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS); for safety: type, number, and grade of adverse events (AEs). Results: A total of 17 studies were analyzed. Anti-PD1 (pembrolizumab, nivolumab, cemiplimab, balstilimab, and tislelizumab), anti-PD-L1 (atezolizumab), and anti-CTLA-4 (ipilimumab, zalifrelimab) agents were employed both as single agents or combinations. Overall ORR ranged from 0% to 65.9%. ORR ranged from 5.9% to 69.6% in PD-L1-positive patients and from 0% to 50% in PD-L1-negative patients. DCR was 30.6–94.1%. mPFS ranged from 2 to 10.4 months. mOS ranged from 8 months to not reached. PD-L1 status did not impact survival. A total of 33.9% to 100% of patients experienced AEs. Conclusion: Immunotherapy represents an appealing strategy for patients with advanced CC, as 2 out of 3 patients seem to respond to ICIs. PD-L1 status might be an indicator of response without impacting survival.