Paclitaxel and cisplatin/carboplatin plus tislelizumab in young patients with cervical cancer preserve fertility: Phase II prospective, single arm clinical study.
Authors: Xu Xingyuan , Yang Zhuo , Dong Yue , Zhu Yanmei , Tian Nan , Wang Danbo 
Published: July 2024

e17513

Background: Cervical function damage after fertility-sparing surgery has a lower pregnancy success rate. Chemotherapy (chemo) mainly plays an auxiliary role in the treatment of cervical cancer (CC), but its efficacy is limited. Recently, immunotherapy has shown remarkable progress in treatment of CC, potentially provide new treatment options for pts of childbearing age who require preservation of fertility. Herein, we conducted this study to evaluate the efficacy and safety of chemo plus tislelizumab (TIS) in young pts with CC who required fertility preservation. Methods: In this single arm, phase II trial, pts with histologically confirmed invasive, FIGO2018 stage IB1-IB3 or IIIC1r (localized cervical lesions) CC, and having fertility needs were enrolled. Eligible pts received 4 cycles chemo (175 mg/m2 paclitaxel + 70 mg/m2 cisplatin/AUC 5-6 carboplatin, Q3W) + TIS (200 mg, Q3W), followed by surgery-diagnostic cervical conization and sentinel lymph node (SLN) biopsy (IIIC1r stage with pelvic lymph node [PLN] systematic dissection)-upon achieving a radiographic complete response (CR). After surgery, pts will undergo 2-cycle chemo plus TIS therapy, if PLNs achieve a pathological complete response (pCR), regardless of the pCR status of localized cervical lesion. If the first cervical conization did not result in a pCR for localized cervical lesion only, a second conization was performed after 2-cycle chemo + TIS. Upon achieving pCR in both the cervical local disease and PLN, maintenance therapy (MT) with TIS will be continued for 1 year. Primary endpoint is pCR (SLN/PLNs + cervical conization) after surgery. The key secondary endpoints included clinical response to 4 cycles chemo + TIS, pregnancy rate, fertility rate, and treatment-emergent adverse events (TEAEs). Results: Between March 2022 and January 2024, 7 pts (mean age 31 years, range 27-38) were enrolled, with 2 pts (28.6%) having stage IIIC1r disease. All 7 pts received chemo plus TIS therapy; of these, 5 (71.4%) pts completed 4 cycles The objective response was achieved in 5 pts, with all complete response. Amenorrhea was observed in 3 of 5 pts (60%), with 2 recovering normal menstruation after chemo cessation, and 1 had finished the last chemo+TIS for 3 weeks and had not yet returned. During 4 cycles chemo + TIS therapy (n=7), the most common TEAEs of any grade were rash (71.4%), alanine aminotransferase increased (57.1%), neutrophil count decreased (57.1%), and white blood cell count decreased (57.1%). At data cutoff (median follow-up, 9 months, range 3.5-17), 1 pt experienced disease progression during MT, and 1 pt got pregnancy 3 months after completed MT. Conclusions: Chemo plus TIS could mediate tumor regression and eliminate micro-metastases with a tolerable safety profile, potentially allowing for fertility preservation in many pts for which this was not thought to be an option. Clinical trial information: ChiCTR2300067495.