Tislelizumab plus chemotherapy shows numerically prolonged PFS in advanced ovarian cancer, modulating immune responses

Despite an initial 80% response rate to platinum-taxane chemotherapy, epithelial ovarian cancer (EOC) remains a highly lethal gynecologic malignancy due to frequent recurrence and reduced platinum sensitivity. Current standard-of-care often falls short in achieving durable remission for advanced stages. Immunotherapy, particularly PD-1 blockade, holds promise by enhancing anti-tumor immunity, but its efficacy and immune modulation in the neoadjuvant setting for EOC have been uncertain, prompting investigation into combination strategies.

The NAIVE trial (NCT04815408), a prospective phase II study, evaluated neoadjuvant platinum-based chemotherapy combined with tislelizumab (NACI) against chemotherapy alone (NAC) in 25 patients with FIGO IIIC-IV EOC. Patients received either NACI or NAC, with the primary endpoint being the 1-year progression-free survival (PFS) rate. Secondary endpoints included overall PFS, R0 resection rates, clinical and pathological responses, and safety. Immune profiling utilized single-cell RNA sequencing and CyTOF to identify mechanistic signatures.

After a median follow-up of 30.7 months, NACI was associated with numerically prolonged progression-free survival (27.2 months vs. 21.8 months for NAC; HR = 0.44, 95% CI 0.15-1.26; P = 0.127), though without statistical significance. NACI also demonstrated higher 1-year PFS (92.3% vs. 83.3%) and 2-year PFS (62.3% vs. 31.8%) rates.

NACI yielded superior tumor responses, including a higher overall response rate (69.2% vs. 58.3%), more R0 resections, and increased pathological complete response rates (CRS3). No unexpected safety signals emerged, and immune-related adverse events were manageable. Mechanistic analyses revealed that NACI responders exhibited heightened CD8+ T-cell-mediated toxicity and metabolic fitness, while nonresponders showed exhaustion phenotypes. Furthermore, response correlated with enrichment of the CXCL13+Th1-GC B-cell-tertiary lymphoid structure (TLS) axis, alongside increased TLS activity and differentiation to IgG-producing plasma cells.