Avelumab with axitinib in persistent or recurrent cervical cancer after platinum-based chemotherapy (ALARICE study).
Authors: Tse Ka Yu , Chu Mandy Man Yee , Ngu Siew Fei , Kwok Gladys Suk Tak , Lau Lesley Suk Kwan , Wei Na , Chan Wai Sun , Liu Stephanie Si , Siu Steven Wai Kwan , Yeung Amy Nga Yan , Soong Inda Sung , Lee Elaine Yuen Phin , Ip Philip Pun Ching , Cheung Annie Nga Yin , Ngan Hextan Yuen Sheung , Chan Karen Kar Loen 
Published: June 2024

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Background: Platinum-based chemotherapy with or without bevacizumab and pembrolizumab is the standard treatment option for advanced or recurrent cervical cancer. However, immunotherapy is only approved for PD-L1 positive tumors. This study aimed to evaluate the efficacy and tolerability of avelumab and axitinib in persistent or recurrent cervical cancer irrespective of PD-L1 status. Methods: This is a phase 2, single-arm, Simon’s 2-stage, pilot study. Eligible patients with cervical cancer after at least one line of platinum-based chemotherapy, not previously exposed to immunotherapy, received avelumab (10 mg/kg) every two weeks and axitinib 5 mg BD at 4-weekly cycle for 12 cycles unless there was disease progression or intolerable side effects. The primary objective was to determine the objective response rate (ORR). Results: 21 patients were enrolled in the study during Jun 2019 to May 2022. The median age was 57 (range 37-78). 11 patients (52.4%) had squamous cell carcinoma, and 15/17 (88.2%) had PD-L1 combined positive score >1. The median number of lines of chemotherapy was 1 (range 1-2), and the median number of cycles of avelumab received was 9 (range 2–12). The study ended prematurely because the pre-specified endpoint was reached in the first stage. The ORR assessed by an independent radiologist was 33.3% (7/21) and disease-control rate was 52.4% (11/21) in the intention-to-treat group, and 38.9% and 61.1%, respectively, in the per-protocol group where three patients did not have follow-up scans. 4 patients had complete response, and 2 remained disease-free even without any treatment after completion of the study drugs. The median duration of response of the whole cohort was 14.3 months (range 11.0-32.2 months). 4 of the responders were platinum-resistant. The median progression-free survival from the first day of avelumab was 10.7 months (95% CI 3-18.5) and overall survival was 20.9 months (95% CI 6.6-35.2). Two pre-specified safety reviews were performed after recruiting the 5th and the 10th patients, and there were excessive serious adverse events that were concerning. All patients experienced adverse events, and the most common included grade 1-2 skin rash (52.4%) and proteinuria (42.9%). 16 patients (76.2%) required to reduce the dosage of axitinib, and the final dose was 2 mg in 8 patients. Using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), EORTC QLQ – Cervical cancer 24 (QLQ-CX24) and EuroQoL EQ-5D-5L questionnaires, no deterioration of patients’ reported outcomes were observed over the study period. Further biomarker analyses are being performed. Conclusions: Avelumab and axitinib could produce a durable and clinically meaningful response in cervical cancer irrespective. These results supported further evaluation of this combination in recurrent or even primary cervical cancer. Clinical trial information: NCT03826589 .