Camrelizumab/Apatinib Shows Early Activity in Advanced Cervical Cancer

Antitumor activity was demonstrated with the combination of camrelizumab (SHR-1210) and apatinib (Rivoceranib) in patients with advanced cervical cancer along with a manageable toxicity profile, according to findings from a phase 2 clinical trial.

The study findings were recently reported in a post during the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program by Chunyan Lan, MD, of the Sun Yat-sen University Cancer Center in Guangzhou, China.

In the treatment landscape for advanced cervical cancer, no approved options exist for patients after first-line treatment. Based on prior research indicating that combination VEGF and PD-1/PD-L1 inhibition is effective, this clinical trial ensued with patients aged 18 to 70 years who had histologically confirmed metastatic, recurrent, or persistent cervical cancer and who progressed on at least one line of systemic therapy. Patients were required to have measurable disease per Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1; an ECOG performance status of 0 or 1; a life expectancy of at least 12 weeks; and adequate bone marrow, renal, blood coagulation, cardiac, and liver function.

Patient characteristics for the 45 enrolled participants were identified at baseline and showed a median age of 51 years (range, 33-67). Most patients (77.8%) had an ECOG performance status of 1. Histology screening showed squamous cell carcinoma in 66.7% of patients and adenocarcinoma in 33.3% of patients. In terms of location of metastases, the majority of the study population had distant lymph node metastases (53.5%); however, there was also a large percentage of subjects with lung metastases (44.4%), pelvic metastases (44.4%), and pelvic lymph node metastases (31.3%).

An equal percentage (42.2%) of patients who received 1 or 2 previous lines of therapy was observed at baseline, with 93.3% having received prior platinum-based chemotherapy and 22.2% had received prior treatment with bevacizumab (Avastin). Positive p16 expression was detected in 60.0% of patients, while 22.2% were negative, and 17.8% were unknown. Regarding PD-L1 expression, 66.7% of patients were positive, 22.2% were negative, and 11.1% were unknown.

Overall, 45 patients were enrolled and 42 were included in the efficacy analysis. Confirmed objective responses were observed in 55.6% of patients (n = 25), which included complete responses (CRs) in 4.4% and partial responses (PRs) in 51.1%. Treatment with the camrelizumab combination led to stable disease (SD) in 26.7% of patients, while 8.9% had progressive disease, and another 8.9% were not evaluable for response. The median duration of response was not reached. Disease control was achieved in 37 out of 42 patients, achieving a disease control rate of 88.1%.

Changes in target lesion size from baseline were assessed for the best response in 42 of the 45 patients. Thirty-three patients (73.3%) had a decrease in target lesion size compared with their baseline measurement. Of the patients with a change in target lesions size, more were PD-L1and p16 positive than negative.

Nineteen progression-free survival (PFS) events were observed in the study. The median PFS was 7.6 months (95% CI, 5.8 months to not reached [NR]). At 6 months, the PFS rate was 58% (95% CI, 44%-76%).

Overall survival (OS) events were reported in 8 patients (19%), but the median OS was NR. At 8 months, the OS rate was 80% (95% CI, 68%-95%).

An exploratory analysis measured differences in response and survival based on PD-L1 expression. Among patients who were positive for PD-L1 expression, 69% had a response to camrelizumab plus apatinib compared with only 50% of those with negative PD-L1 expression (P = .281). PFS was higher among individuals with PD-L1 positivity at 9.6 months (95% CI, 7.6-NR) versus 5.3 months (95% CI, 2.0-NR). The difference in PFS was significant (P = .017).

In the safety assessment, 96% of patients were reported to have at least 1 treatment-related adverse event (TRAE). The most frequent grade 1/2 TRAEs were hypertension (60%), proteinuria (56%), aspartate aminotransferase increase (45%), and anemia (40%). Frequent grade 3/4 TRAEs were hypertension (24%), anemia (20%), and fatigue (16%).

Immune-related AEs were most low grade. Grade 1/2 events mainly included hypothyroidism (22%), reactive cutaneous capillary endothelial proliferation (9%), and rash (4%). The grade 3/4 immune-related AEs were rash, neutropenia, and anemia, which occurred in 2% of patients each.

The study of camrelizumab plus apatinib in advanced cervical cancer is an ongoing, open-label, single-arm, multicenter study investigating the efficacy and safety of the combination. The primary end point is ORR. The study is also investigating PFS, OS, 6-month PFS rate, 9-month OS rate, duration of response, and incidence of AEs as secondary end points.

A Simon’s 2-stage optimal design was followed in this study and was 80% powered to test the null hypothesis that the objective response rate would be 17% versus the 35% option.

Patients in the study received intravenous camrelizumab 200 mg once every 2 weeks combined with oral apatinib 250 mg once daily. The treatment cycle was 4 weeks, and patients could continue camrelizumab for up to 24 months. For both drugs, treatment was continued until disease progression.

The investigators suggested that further study of the combination was warranted in larger cervical cancer populations based on the positive findings in this study.

_Reference:

_{Lan C, Huan X, Shen JX, et al. Camrelizumab plus apatinib in patients with advanced cervical cancer: A multicenter, open-label, single-arm, phase II trial. J Clin Oncol. 2020;38(suppl):6021. doi:10.1200/JCO.2020.38.15_suppl.6021}