Efficacy and Safety of Sintilimab Plus Anlotinib for PD-L1–Positive Recurrent or Metastatic Cervical Cancer: A Multicenter, Single-Arm, Prospective Phase II Trial

Abstract

PURPOSE No combined immunotherapy and antiangiogenic therapy have been investigated in exclusively programmed death-ligand 1 (PD-L1)–positive advanced cervical cancer (CA). We investigated the efficacy and safety of sintilimab plus anlotinib as second-line or later therapy for PD-L1–positive recurrent or metastatic (R/M) CA. PATIENTS AND METHODS Patients with PD-L1–positive (Combined Positive Score ≥ 1) R/M CA who progressed after at least one prior systemic chemotherapeutic regimen or could not tolerate chemotherapy were eligible for the phase II trial. The patients received 200 mg sintilimab once on day 1 and 10 mg anlotinib once daily on days 1-14 every 3 weeks. The primary end point was investigator-confirmed objective response rate (ORR) per RECIST v1.1. Secondary end points included progression-free survival (PFS), overall survival, and disease control rate. Biomarkers were explored. RESULTS Forty-two patients were enrolled. The ORR was 54.8% (95% CI, 38.7 to 70.2). In 39 efficacy-evaluable patients, the ORR was 59.0% (95% CI, 42.1 to 74.4); the disease control rate was 94.9% (95% CI, 82.7 to 99.4). The median PFS was 9.4 months (95% CI, 8.0 to 14.6). The median overall survival was not reached. Furthermore, 85.8% of the patients experienced treatment-related adverse events. The most frequent treatment-related adverse events were hypothyroidism (33.3%), elevated aspartate aminotransferase levels (21.4%), and hypertension (19.0%). Patients with altered PIK3CA, PI3K-AKT signaling, or KMT2D had a higher ORR, whereas those with altered STK11 and/or JAK2 had a significantly shorter PFS. CONCLUSION Sintilimab plus anlotinib as second-line or later therapy is efficacious and safe for patients with advanced CA who have failed prior chemotherapy.

Efficacy of Immunotherapy Combined with Antiangiogenic Therapy in Treatment-Failure Patients with Advanced Carcinoma Ex Pleomorphic Adenoma of the Submandibular Gland: A Case Report

“…Therefore, based on this consideration, we expect that this patient would also benefit from the combination of immune checkpoint inhibitors with antiangiogenic drugs for survival. In advanced NSCLC [ 29 ] and cervical cancer [ 30 ], sintilimab, in combination with anlotinib, exerts synergistic antitumor effects. However, treatment of advanced Ca ex PA with immunotherapy plus antiangiogenic therapy is not yet reported.…”

Mechanisms of tumor resistance to immune checkpoint blockade and combination strategies to overcome resistance

“…Noteworthily, plenty of clinical trials are exploring the combination strategies of angiogenesis inhibitors and anti-PD-1/PD-L1 at present. The preliminary data of some combinations demonstrated favorable therapeutic effects such as camrelizumab plus apatinib in advanced triple-negative breast cancer (NCT03394287), advanced cervical cancer (NCT03816553), and advanced HCC (NCT03463876) and sintilimab plus anlotinib in advanced NSCLC (NCT03628521) and PD-L1-positive recurrent or metastatic cervical cancer ( 284 ). Subsequent phase 3 trials are necessary to confirm the effectiveness of these combination regimens.…”

PD-1/PD-L1 inhibitors for advanced or metastatic cervical cancer: From bench to bed

“…To date, 15 clinical trials have reported their findings for cervical cancer (Table 1), while another two clinical trials (78,79) are ongoing for advanced or metastatic cervical cancer. Among the reported clinical trials, two focused on pembrolizumab (16,17,(69)(70)(71), three on nivolumab (18-20), one on sintilimab (72), two on balstilimab (73,74), one on camrelizumab (75), two on cemiplimab (76, 77), one on atezolizumab (21). Afterwards, we would review the outcomes of pembrolizumab, nivolumab, and atezolizumab in detail and also prospect the ongoing clinical trials.…”