Long-term survival outcomes and immune checkpoint inhibitor (ICI) retreatment in patients with advanced cervical cancer who received camrelizumab plus apatinib in the CLAP study.
Authors: Lan Chunyan , Lu Huaiwu , Liu Junxiu , Tong Chongjie , Liang Haixi , Peng Hongyu , Zhou Lin , Yang Ting , Xu Qin , Huang Xin 
Published: June 2023

e17513

Background: Camrelizumab (a programmed death 1 [PD-1] inhibitor) plus apatinib (a vascular endothelial growth factor receptor 2 [VEGFR2] inhibitor) showed promising efficacy and safety profiles in patient with advanced cervical cancer in the CLAP study (NCT03816553). Herein we present updated efficacy and safety data with more than 24 months of additional follow-up, and outcomes for patients retreated with ICIs following disease progression. Methods: In this single-arm phase 2 trial, 45 patients received camrelizumab (200 mg intravenously, q2w) and apatinib (250 mg orally, qd) on a 4-week cycle until disease progression, unacceptable toxicity, withdrawal of consent, or up to 2 years. For patients who completed 2 years treatment and were considered to benefit from continuing treatment, a one-year extension treatment would be provided if the patients agreed. Results: At the data cutoff (August 31, 2022), the median duration of follow-up was 11.9 (range, 1.0–43.9) months. Nine (20.0%) patients completed 2-year treatment (eight entered the one-year extension treatment, of which five completed and three discontinued due to disease progression) and 36 (80.0%) discontinued treatment (24 [53.3%] disease progression, 4 [8.9%] adverse events, 5 [11.1%] patient refusal, and 3 [6.7%] withdrawal of consent). The median duration of treatment was 6 (range, 0.9–37.4) months. The confirmed objective response rate was 55.6% (95% CI: 40.0, 70.4) that was unchanged from previous report, including two (4.4%) complete response (CR) and 23 (51.1%) partial response (PR). The median duration of response was 16.6 (95% CI, 5.6–29.9) months among 25 responders. Median progression-free survival (PFS) was 8.9 (95% CI, 5.6–18.1) months; the 12-month PFS rate was 40.7% (95% CI, 25.2–55.6). The median overall survival (OS) was 15.9 (95% CI, 9.3–36.9) months; the 24-month OS rate was 46.4% (95% CI, 30.1–61.1). Age > 50, programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 1, CPS ≥ 10, TMB-high, and PIK3CA mutation were associated with longer OS. Seven patients were retreated with the same or other ICIs after disease progression. All of them showed initial response (one CR and 6 PR) to study treatment, then had progressive disease (PD) and discontinued treatment. Of the seven patients, six achieved stable disease and one had PD following ICIs retreatment. Four patients died and three were alive at the data cutoff. Two patients received ICIs retreatment for more than 20 months, one of which was still on ICIs retreatment. No new safety signals were identified with additional 24-month follow-up. Conclusions: This long-term follow-up data demonstrate sustained and durable efficacy of camrelizumab plus apatinib, with no new safety signals, in patients with advanced cervical cancer who progressed after prior platinum-based chemotherapy. Clinical trial information: NCT03816553 .