Efficacy and Prognostic Factors for Response to PD-1 Inhibitors in Advanced Cervical Carcinoma: A Retrospective Study

Abstract

Purpose: Programmed cell death protein 1 (PD-1) inhibitors have shown a therapeutic effect in the treatment of advanced cervical cancer in clinical trials. However, the clinical characteristics associated with response remain undetermined. This study aimed to evaluate the efficacy and prognostic factors of PD-1 inhibitors in patients with advanced cervical cancer in clinical practice.

Patients and methods: The study enrolled patients with recurrent or metastatic cervical cancer treated with PD-1 inhibitors at our center between March 2018 and November 2020. The primary outcomes were the objective response rate (ORR) and progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety. In addition, independent prognostic factors were identified by multivariate regression analysis.

Results: A total of 102 patients were included, and the ORR and disease control rate (DCR) were 51.0% and 66.7%, respectively. Median PFS was 11.0 months (95% CI, 1.7-20.4), while median OS was not achieved. Multivariate analysis indicated that factors associated with a better prognosis (ORR and PFS) included squamous cell carcinoma, a time to recurrence >6 months, and PD-1 plus chemotherapy and anti-angiogenic drugs (p < 0.05). Lines of therapy were independent factors for ORR but not for PFS. We also observed a tendency for longer PFS in patients with lung metastases and lymph node metastases only. Treatment-related adverse events (AEs) were well tolerated and primarily included thrombocytopenia, hepatic dysfunction, anemia, and leukopenia.

Conclusion: PD-1 inhibitors demonstrated beneficial efficacy and safety in advanced cervical cancer, particularly for patients with squamous cell carcinoma, a time to recurrence >6 months, or PD-1 plus chemotherapy and anti-angiogenic drugs. Further studies are needed to confirm the long-term outcomes.

Keywords: PD-1; anti-angiogenic therapy; cervical cancer; chemotherapy; immune checkpoint inhibitors.

Figure 1

Flow diagram of patient selection. *Thirteen patients withdrew treatment, eight of whom did not continue treatment due to financial problems, and five failed to complete treatment due to COVID-19.

Figure 2

Kaplan–Meier plot of progression-free survival (A) and overall survival (B) in all patients; Kaplan–Meier plot of progression-free survival by clinical factors, (C) histology, (D) time to recurrence, and (E) treatment pattern. NR, not reached; OS, overall survival; PD-1, programmed death-1; PFS, progression-free survival.

Figure 3

(A) Duration of responses in patients who achieved an objective response. The swimmer plots show the time to first response and the duration of the first response. (B) Waterfall plot of the best percentage change in tumor size from baseline. CR, complete response; PR, partial response.

Figure 4

Chest computed tomography images at baseline, cycles 2 and 4 are shown for a 49-year-old woman with squamous cervical cancer who developed lung metastasis after 9 months of first-line systemic therapy. She was treated with camrelizumab combined with paclitaxel, cisplatin, and apatinib for four cycles, followed by camrelizumab and apatinib as maintenance therapy. Tumor lesions in her lung clearly shrank after two cycles and were significantly reduced after four cycles.