Combination therapies for the treatment of locally advanced and advanced cervical cancer

Cervical cancer remains a significant global health challenge. This narrative review synthesizes evidence from PubMed/MEDLINE, Embase, and ClinicalTrials.gov (January 2010 to August 2026), focusing on randomized prospective trials of systemic combination therapies.

In locally advanced cervical cancer, pivotal phase 3 trials such as INTERLACE (induction chemotherapy) and KEYNOTE-A18 (pembrolizumab plus chemoradiation) have shown improved survival. For advanced, persistent, recurrent, or metastatic disease, adding pembrolizumab (KEYNOTE-826) or atezolizumab (BEATcc) to chemotherapy, with or without bevacizumab, has increased median overall survival from 26 to over 37 months. In the second-line setting, tisotumab vedotin (innovaTV 301) has become a new Category 1 standard. Emerging strategies include neoadjuvant chemoimmunotherapy to downstage isolated pelvic recurrences for extended resection (LEER), regional dual-checkpoint blockade (cadonilimab), TROP2-directed antibody-drug conjugates (sacituzumab tirumotecan), and therapeutic vaccines.

Immune checkpoint inhibitors and antibody-drug conjugates have improved survival; however, high costs limit access, especially in low- and middle-income countries where disease burden is greatest. Key priorities include harmonizing predictive biomarkers, managing overlapping toxicities, and designing resource-conscious cooperative trials to evaluate shorter or lower-dose maintenance regimens. Addressing access disparities while refining patient selection is essential to achieving equitable global care.