Oncology · Medical Literature
Neoadjuvant tislelizumab (anti-PD-1 antibody) plus chemotherapy in patients with advanced epithelial ovarian cancer: the exploratory NAIVE trial.
Abstract
The clinical efficacy and immune modulation of neoadjuvant immunochemotherapy for epithelial ovarian cancer (EOC) remain uncertain. To clarify these effects, the NAIVE trial (NCT04815408), a prospective phase II study, evaluated the efficacy of neoadjuvant platinum-based chemotherapy with tislelizumab (NACI) in comparison with chemotherapy alone (NAC) in patients with FIGO IIIC-IV EOC. The primary endpoint was the 1-year progression-free survival (PFS) rate; the secondary endpoints included PFS, R0 resection, clinical and pathological responses, and safety. Between April 2021 and July 2024, 25 patients were included in the final analysis. After a median follow-up period of 30.7 months, NACI was associated with numerically prolonged progression-free survival (27.2 vs. 21.8 months; HR = 0.44, 95% CI 0.15-1.26; P = 0.127), with higher 1-year (92.3% vs. 83.3%) and 2-year (62.3% vs. 31.8%) PFS rates than NAC. NACI also yielded superior tumor responses, including higher ORR (69.2% vs. 58.3%), more R0 resections, and increased CRS3 rates. No unexpected safety signals emerged, and immune-related adverse events were manageable. Immune profiling techniques, such as single-cell RNA sequencing and CyTOF, identified distinct signatures. NACI responders demonstrated heightened CD8+ T-cell-mediated toxicity and metabolic fitness, whereas nonresponders exhibited exhaustion phenotypes. Furthermore, the response correlated with enrichment of the CXCL13+Th1-GC B-cell-tertiary lymphoid structure (TLS) axis, accompanied by increased TLS activity and differentiation to IgG-producing plasma cells. Overall, NACI yielded PFS trends with acceptable safety, but without statistical significance. The mechanistic analyses highlight the role of the CXCL13+Th1-GC B-cell-TLS axis as a potential biomarker and driver of therapeutic response.
Clinical relevance
In patients with advanced epithelial ovarian cancer (FIGO IIIC–IV), does the addition of tislelizumab (anti-PD-1) to neoadjuvant platinum-based chemotherapy improve progression-free survival and surgical outcomes compared with platinum-based chemotherapy alone? __SNAPSHOT__ {"studyDesign":"Prospective, randomized, exploratory Phase II trial (NCT04815408)","setting":"Not reported (single-center or multicenter not specified in abstract; trial registered in China)","sampleSize":"n=25 total (NACI arm: n=13; NAC arm: n=12, inferred from reported percentages — calculated)","population":"Adults with FIGO stage IIIC–IV epithelial ovarian cancer eligible for neoadjuvant chemotherapy followed by interval debulking surgery","intervention":"Neoadjuvant platinum-based chemotherapy plus tislelizumab (anti-PD-1 antibody) — NACI","comparator":"Neoadjuvant platinum-based chemotherapy alone — NAC","primaryOutcome":"1-year progression-free survival (PFS) rate","followUp":"Median 30.7 months","fundingSource":"Not reported"}
Key findings
After a median follow-up of 30.7 months, the primary endpoint (1-year PFS rate) was 92.3% in the NACI arm versus 83.3% in the NAC arm (difference not reported with formal statistical testing for primary endpoint). Median PFS was numerically longer with NACI (27.2 vs. 21.8 months; HR = 0.44, 95% CI 0.15–1.26; P = 0.127), indicating no statistically significant difference. The 2-year PFS rate was 62.3% (NACI) vs. 31.8% (NAC) — an absolute difference of approximately 30.5 percentage points (calculated), though formal p-values for these rates were not reported in the abstract. The objective response rate (ORR) was 69.2% (NACI) vs. 58.3% (NAC); the magnitude of difference and p-value were not reported. NACI also yielded higher rates of R0 resection and complete resection score 3 (CRS3) compared with NAC; exact figures and statistical significance were not reported in the abstract. No unexpected safety signals were identified; immune-related adverse events were described as manageable. NNT cannot be calculated from available data. The trial also conducted exploratory immune profiling (methodology not fully described in the available abstract).
Practice implications
The NAIVE trial provides preliminary signal that adding tislelizumab to neoadjuvant platinum-based chemotherapy may improve PFS and surgical outcomes in FIGO IIIC–IV epithelial ovarian cancer. However, the primary endpoint difference (1-year PFS: 92.3% vs. 83.3%) was not subjected to a reported formal statistical test, and the key PFS HR of 0.44 did not reach statistical significance (P = 0.127; 95% CI 0.15–1.26 crosses unity). The 2-year PFS difference (approximately 30.5 percentage points) is numerically compelling but must be interpreted with extreme caution given the very small sample size. The study was explicitly described as 'exploratory,' meaning it was not powered to confirm efficacy. Findings cannot be generalized to the broader advanced EOC population without larger, adequately powered trials. Patients who were not adequately represented include those with specific molecular subgroups (e.g., BRCA-mutated, HRD status), elderly patients, and non-Asian populations. The biological plausibility is supported by exploratory immune profiling, but this remains hypothesis-generating. IMPORTANT CAVEAT: Only the abstract was available for this summary; full methodology, randomization details, stratification factors, and complete adverse event data could not be reviewed, which substantially limits interpretation. __LIMITATIONS__ Critically underpowered: n=25 total, rendering all between-arm comparisons highly susceptible to Type I and Type II error,The primary endpoint (1-year PFS rate) was not formally compared with reported p-values, limiting interpretation of the central finding,The PFS hazard ratio (HR 0.44; 95% CI 0.15–1.26) did not achieve statistical significance (P=0.127); the wide CI reflects extreme imprecision due to sample size,Exploratory phase II design — not powered or intended to confirm efficacy; results are hypothesis-generating only,Blinding status not reported in the abstract; open-label design is possible and would introduce performance and assessment bias,Short follow-up relative to ovarian cancer natural history limits assessment of OS benefit,Selection bias and generalizability are uncertain; trial was conducted in China with no description of institutional setting,Funding source not reported; potential for undisclosed conflicts of interest cannot be excluded,Molecular biomarker data (BRCA, HRD status) and their interaction with treatment effect were not reported in the abstract,No NNT or NNH calculable from available data,Full safety data not available from abstract alone; immune-related AE grading and rates not quantified __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ The NAIVE trial is a small, exploratory Phase II study (n=25) suggesting that adding tislelizumab to neoadjuvant platinum-based chemotherapy may improve PFS and surgical resectability in FIGO IIIC–IV epithelial ovarian cancer, but the primary endpoint did not achieve statistical significance and the trial was not powered to confirm efficacy. These results are hypothesis-generating and should not alter current clinical practice. Adequately powered, Phase III confirmatory trials are required before this strategy can be recommended.