Efficacy and safety of sintilimab plus paclitaxel and cisplatin as neoadjuvant therapy for locally advanced cervical cancer: A phase II trial.

person Ting Wan Department of Gynecologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China info_outline Ting Wan, He Huang, Yanling Feng, Jundong Li, Min Zheng, Yifan Meng, Jihong Liu

Authors person Ting Wan Department of Gynecologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China info_outline Ting Wan, He Huang, Yanling Feng, Jundong Li, Min Zheng, Yifan Meng, Jihong Liu Organizations Department of Gynecologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China, Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China, Department of Gynecologic Oncology, Sun Yet Sen University Cancer Center, Guangzhou, China Abstract Disclosures Research Funding Innoventbio Background: The KEYNOTE 826 study has demonstrated significant survival benefits with first-line pembrolizumab (anti PD-1) plus chemotherapy for recurrent/metastatic cervical cancer (CC). This phase II study aims to evaluate the efficacy and safety of Sintilimab (anti PD-1) plus paclitaxel and cisplatin as neoadjuvant therapy for locally advanced CC. Methods: Patients with newly confirmed locally advanced CC (stage IB3 or IIA2) received neoadjuvant chemotherapy with paclitaxel (150mg/m2, iv) and cisplatin (70mg/m2, iv) plus Sintilimab (200mg, iv) Q3W for 3 cycles, followed by radical surgery. The patients evaluated PD without distant metastases after 2 cycles of neoadjuvant therapy underwent surgery immediately. The primary endpoint was pathological complete remission rate (pCR). Secondary endpoints included ORR, PFS, 2-years PFS rate and adverse events (CTCAE 5.0) and biomarker exploration. Results: As of data cutoff on Feb 1st, 2024, 47 eligible patients were enrolled, 44 patients received 3 cycles of neoadjuvant therapy, 43 patients then underwent radical surgery and were evaluable. The primary endpoint of pCR rate was 32.6% (14/43), optimal remission rate (residual tumor cells with a depth of less than 3mm) was 51.2% (22/43). Except for one patient with SD, 42 had objective responses (97.7%). At the date cutoff, the median follow-up time was 17 months (range 1-35), two patients who evaluated as PR after neoadjuvant therapy were recurred, one with distant lymph node recurrence, and the other with lung metastasis. In terms of hematological toxicity, 15 patients presented with grade 3-4 neutropenia and no other grade 3-4 adverse events. Possible immune-related side effects included skin rash (17/47, G1-2), alanine aminotransferase increased (8/47, G1), hypothyroidism (6/47, G1-2), creatinine increased (5/47, G1), and hyperlipidemia (1/47, G1). Conclusions: Sintilimab plus paclitaxel and cisplatin as neoadjuvant therapy showed encouraging antitumor activity with 32.6% pCR rate and manageable toxicities in patients with locally advanced CC. Clinical trial information: NCT04799639.

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