Neoadjuvant camrelizumab plus chemotherapy for locally advanced cervical cancer (NACI study): A prospective, single-arm, phase II trial.

Abstract

5520 Background: First-line treatments for locally advanced cervical cancer (LACC) have limited efficacy and neoadjuvant chemotherapy (NACT) is an emerging approach, however, two-thirds of patients (pts) respond to it and pts without response benefit little. PD-1 inhibitors have shown promising role in recurrent or metastatic cervical cancer. This study aims to evaluate the efficacy and safety of preoperative PD-1 inhibitor camrelizumab combined neoadjuvant therapy for LACC. Methods: The study is designed as a multicenter, open-label, single-arm, prospective phase II study. Pts are enrolled if they had previously untreated LACC (2018 FIGO staged IB3, IIA2 and IIB/IIIC1r (tumor size > 4cm). Eligible pts will receive neoadjuvant chemo-immunotherapy (NACIT), defined as one cycle of cisplatin (75-80 mg/m2, iv) plus nab-paclitaxel (260 mg/m2, iv) NACT and subsequent two cycles of camrelizumab (200mg, iv) combined NACT. Either surgery or concurrent chemoradiotherapy are conducted according to the response as per the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. The primary endpoint was objective response rate (ORR), and the secondary endpoints were pathological complete remission (pCR) rate, rate of postoperative adjuvant treatment, event-free survival, overall survival and safety. Results: From Dec 1, 2020 to Feb 1, 2023, 83 pts were enrolled, and 78 pts were evaluated for response. The ORR was 100% (95%CI, 95.38 to 100), with 14 (17.95%) complete response (CR) and 64 (82.05%) partial response. Regarding the pathological findings of 76 pts who underwent radical surgery, 30 (39.47% (95%CI, 28.44 to 51.35)) pts achieved pCR, while 17 (22.37%) needed postoperative adjuvant treatment as indicated in NCCN guideline, of who 14 had positive pelvic nodes, positive surgical margin, and/or positive parametrium and the other three met Sedlis criteria. RECIST CR was significantly associated with pCR ( P = 0.016). Pre-treatment PD-L1 expression (Combined Positive Score) was a predictive biomarker for RECIST CR ( P = 0.036) but not for pCR ( P = 0.078) in these evaluated patients. Grade 3 or 4 treatment-related adverse events occurred in 35 (44.87%) pts during NACIT; the most common were lymphocytopia (25.64%), neutropenia (12.82%) and leucopenia (8.97%). Conclusions: NACIT for LACC demonstrated extremely high ORR and pCR rate with manageable toxicity profile, and greatly reduced the need of postoperative adjuvant therapy. Clinical trial information: NCT04516616 .