Neoadjuvant Tislelizumab Plus Chemotherapy Shows Promising Activity in Locally Advanced Cervical Cancer

The combination of tislelizumab (Tevimbra), a monoclonal antibody, plus chemotherapy revealed encouraging antitumor activity in patients with locally advanced cervical cancer, according to findings from a single-arm phase 2 NATIC trial in China (ChiCTR2200065392).

Among 30 enrolled patients, 20 achieved a pathologic complete response (pCR), yielding a pCR rate of 66.7% (95% CI, 48.8%–80.8%), whereas 4 patients attained a major pathologic response (MPR; 13.3%). Comparatively, in prior trials, investigators reported platinum-based neoadjuvant chemotherapy pCR rates ranging from 8.5% to 26%.

The objective response rate (ORR) was 90.0% (95% CI, 74.4%–96.5%), consisting of 17 (56.7%) complete responses and 10 (33.3%) partial responses. Notably, pCR was significantly associated with higher PD-L1 combined positive scores (CPS; median 77.5 vs 8.5; P <.001) and longer time to surgery (median 40.4 vs 28.2 days; P =.041).

At the data cutoff of December 31, 2024, 2 patients developed disease recurrence but no deaths were reported. The 18-month disease-free survival (DFS) rate was 90.0% (95% CI, 77.7%–100.0%), according to Jindong Sheng, MD, and colleagues at Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

All patients completed 3 cycles of neoadjuvant therapy and all underwent surgery. A total of 23 patients completed treatment, 7 patients received adjuvant therapy in the form of chemoradiotherapy (n = 2), radiotherapy (n = 3), or chemotherapy (n = 2). The primary efficacy end point was pCR and secondary end points were optimal pathological response (OPR) and MPR.

The median age was 51.5 years (range, 39.5–57.0), 93.3% had squamous cell carcinoma, and the majority (56.7%) had a CPS of 50 or greater. Notably, even 1 patient with a PD-L1 CPS less than 1 achieved pCR postoperatively with the experimental regimen. Eighty percent of patients had ECOG performance status of 0 (24 of 30). The median tumor size was 4.6 cm (range, 4.2-5.2).

Imaging and pathologic responses were discordant in some cases: 56.7% (17/30) of patients had imaging findings consistent with pathologic response. Seven patients with a partial response on imaging were assessed as pCR pathologically, whereas 5 with complete imaging response had residual viable tumors, including 3 MPR and 2 as non-OPR.

Regarding safety, all patients experienced any grade treatment-related adverse events (TRAEs), with 7 patients experiencing any grade immune-related AEs (irAEs), with 1 grade 3 or higher irAE (Guillain-Barré syndrome).

The most common TRAEs were lymphopenia (90.0%), anemia (70.0%), and hypoalbuminemia (70.0%). A total of 8 (26.7%) patients had grade 3 TRAEs, with no grade 4 TRAEs reported. During neoadjuvant treatment, none of the observed AEs led to discontinuation, dose reduction, or death.

The discrepancy between imaging and pathologic response could be attributed to inherent MRI limitations in distinguishing necrotic tissue, inflammatory changes due to neoadjuvant therapy, and viable neoplastic tissue. The investigators wrote, “Further, the use of more radical surgery, such as type C1 hysterectomy compared with conventional approaches could uncover small disease foci missed by imaging.”

Overall, the study showed a well-tolerated and manageable safety profile for neoadjuvant tislelizumab plus chemotherapy in patients with locally advanced cervical cancer. Safety is consistent with the established toxicity of each agent, and no unexpected toxicities were observed.

REFERENCE

Sheng J, Luo H, Liu X, et al. Tislelizumab (anti-PD-1) plus chemotherapy as neoadjuvant therapy for patients with stage IB3/IIA2 cervical cancer (NATIC): a prospective, single-arm, phase II study. Signal Transduct Target Ther. 2025;10(1):215. Published 2025 Jul 4. doi:10.1038/s41392-025-02294-9