Immunotherapy with anti-PD-1 or PD-L1 in advanced ovarian cancer (OC): A meta-analysis of randomized trials.
Abstract
5570 Background: Immunotherapy (IO) has shown promising results in several solid tumors, including gynaecological malignancies. While PARP inhibitors and bevacizumab had deeply improved outcomes in OC, prognosis remains poor, underscoring the need for innovative treatment strategies. Anti-PD-1 and PD-L1 monoclonal antibodies have been evaluated in randomized trials across both first-line and recurrent OC settings. This meta-analysis summarizes the available evidence to assess progression-free survival (PFS) benefits from IO-based strategies. Methods: Phase II and III randomized clinical trials (RCTs) evaluating IO-based strategies using PD1 or PDL1 inhibitors published between 2019 and 2024 were identified through PubMed, Embase, and the Cochrane Library, as well as conference proceedings. Eight trials with PFS as primary endpoint, conducted in first-line and recurrence settings, were included. Data on PFS by PD-L1 status were available in seven trials. Three trials included two experimental arms and were analysed separately. Hazard ratios (HRs), 95% confidence intervals (CIs), and PFS events were extracted for overall populations and subgroups. A random-effects model was employed for data analysis, with sensitivity analyses performed to explore outcome variability. Results: The meta-analysis included 8 trials comprising 6,205 patients. The addition of IO to chemotherapy or placebo showed no improvement in PFS (HR = 1.02, 95% CI 0.86-1.22). Subgroup analyses indicated no significant differences in PFS in first-line (HR = 0.99, 95% CI 0.78-1.26) or recurrence settings (HR= 1.07, 95% CI 0.80-1.44). In trials reporting PD-L1 status (47.5% PD-L1 positive population), IO-based therapies demonstrated a non-significant trend towards PFS improvement (HR = 0.94, 95% CI 0.77-1.13). Excluding IO-only arms yielded similar results (HR = 0.94, 95% CI 0.79-1.11). Conclusions: IO-based strategies did not provide a substantial PFS benefit in advanced OC, irrespective of disease setting or PD-L1 status. Identifying effective combination strategies and patient subgroups that may benefit from IO remains an open research question.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (20)
Riccardo Vida
Department of Medical Oncology, Centro di Riferimento Oncologico (CRO) - National Cancer Institute, IRCCS Aviano; Department of Medicine (DMED), University of Udine, Udine, Italy
Michele Bartoletti
Marcella Montico
Clinical Trial Office, Scientific Direction, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy., Lucca, Italy
Monica Rizzetto
Department of Medical Oncology, Centro di Riferimento Oncologico (CRO), IRCCS; Department of Medicine (DMED), University of Udine, Udine, Italy
Giulia Zapelloni
Department of Medical Oncology, Centro di Riferimento Oncologico (CRO), IRCCS; Department of Medicine (DMED), University of Udine, Aviano, Italy
Serena Corsetti
Unit of Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano (PN), Lucca, Italy
Milena Nicoloso
Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy
Simona Scalone
Division of Medical Oncology National Cancer Institute Aviano Italy, Aviano, Italy
Anna Del Fabro
Gynecological Surgery Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, National Cancer Institute, Aviano, PN, Italy, Aviano, Italy
Nicolò Clemente
Gynecological Surgery Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, National Cancer Institute, Aviano, PN, Italy, Aviano, Italy
Tommaso Occhiali
Gynecological Surgery Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, National Cancer Institute, Aviano, PN, Italy, Aviano, Italy
Emilio Lucia
Unit of Gynecologic Oncology Surgery, IRCCS CRO Aviano, National Cancer Institute, Aviano, Italy, Aviano, Italy
Claudio Reato
Gynecological Surgery Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, National Cancer Institute, Aviano, PN, Italy, Aviano, Italy
Luca Martella
Gynecological Surgery Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, National Cancer Institute, Aviano, PN, Italy, Aviano, Italy
Elisabetta Caccin
Clinical Trial Office, Scientific Direction, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy, Aviano, Italy
Margherita Poletto
Clinical Trial Office, Scientific Direction, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy, Aviano, Italy
Gianna Tabaro
CRO National Cancer Center, Aviano, Italy
Vincenzo Canzonieri
Pathology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, National Cancer Institute; Department of Medical, Surgical and Health Sciences, University of Trieste, Aviano, Italy
Antonino Ditto
Gynecological Surgery Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, National Cancer Institute, Aviano, PN, Italy, Aviano, Italy
Fabio Puglisi