Anlotinib appeared safe with a manageable toxicity profile as treatment of patients with recurrent advanced cervical cancer in a phase 2 study.
Anlotinib (AL3818) as a single agent demonstrated promising activity as treatment of patients with recurrent advanced cervical cancer in a phase 2 study, meeting the primary end point of objective response rate (ORR) in the study.
According to results presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program, the ORR was 24.4% with anlotinib (95% CI, 12.4%-40.3%), and partial response (PR) was the best response observed, which occurred in 10 patients. Additionally, 14 patients had stable disease (34.2%), and 16 patients had progressive disease (39.0%). One patient was not evaluable (2.4%). The disease control rate was 58.5% (95% CI, 41.1%-73.7%).
Secondary end points of the study included disease control rate, progression-free survival, overall survival, and safety. The median progression-free survival with anlotinib was 3.2 months (95% CI, 0.4-5.9).
Anlotinib appeared safe with a manageable toxicity profile. No unexpected safety signals were observed. Most adverse events (AEs) in the study were grade 1/2, and the most common AEs were anemia (29.3%), hand-foot syndrome (26.8%), lymphocytopenia (24.4%), urinary leukocyte positive (22%), and fatigue (19.5%). Grade 3 AEs observed in the study included urinary leukocyte positive (0.8%), hematuria (4.9%), and hypertension (2.4%).
No treatment-related deaths occurred with anlotinib in this study.
In the prospective, single-arm, single-center study, patients with recurrent or metastatic advanced cervical cancer who had previously received second-line or later therapies received an oral 12-mg dose of anlotinib daily on days 1 to 14 on a 21-day cycle (n = 41). Patients received the therapy until disease progression, death, or intolerable toxicity.
Patients enrolled to the study from December 2018 to October 2019, and the data cut-off date for these results was January 15, 2020. The median follow-up duration was 2.6 months (range, 0.7-10.3).
At baseline, the median age of patients on the study was 53 years, and most patients (n = 34; 82.9%) had squamous cell carcinoma histology; adenocarcinoma histology was observed in 6 patients (14.6%) and other in 1 (2.4%). The ECOG performance status was 0 in 40 patients (97.6%) and 1 in 1 patient (2.4%). The International Federation of Gynecology and Obstetrics stage of disease at initial diagnosis was I in 2 patients (4.9%), II in 25 patients (61.0%), III in 8 patients (19.5%), and IV in 6 patients (14.6%). Twenty-six patients had received more than 2 prior lines of therapy (63.4%) while 15 patients only had 2 prior lines (36.6%). The median time since last treatment was 6.1 months (range, 0.7-44.4).
Patients with recurrent or metastatic cervical cancer have limited effective therapies available, especially in the third-line setting and beyond. However, investigators noted that it is difficult to obtain clinical benefit with chemotherapy after the patient experiences a recurrence or metastasis.
Anlotinib is a novel tyrosine kinase inhibitor that is highly selective for multiple targets, including VEGFR, PDGFR, and FGFR. A prior phase 1 study demonstrated clinical activity with this agent in female patients with genital tumors, while other studies have shown clinical antitumor activity in various cancer types as well. The purpose of this study was to evaluate the efficacy and safety of this therapy as treatment of women with recurrent advanced cervical cancer.
This research warrants further studies of anlotinib in combination with other therapies, such as chemoradiotherapy, targeted therapy, or immunotherapy. These studies should evaluate the efficacy and safety of potential anlotinib combination regimens in patients with cervical cancer.
Wu X. Anlotinib in patients with recurrent advanced cervical cancer: A prospective single-arm, open-label, phase Ⅱ trial. J Clin Oncol. 2020;38(suppl):6034. doi:10.1200/JCO.2020.38.15_suppl.6034