Promising Efficacy/Safety Shown With Anlotinib Plus Sintilimab in Endometrial Cancer

The combination of anlotinib (AL3818) and sintilimab (Tyvyt) showed encouraging antitumor activity with favorable toxicity in patients with recurrent advanced endometrial cancer, according to findings from a phase 2 study.¹

Recurrent advanced endometrial cancer has previously been treated with systemic chemotherapy, but the outcomes observed with this type of treatment are limited. Research on the combination of targeted therapy and immunotherapy has begun with the goal of learning more about the treatment of malignant tumors.

The prospective, open-label, single-arm, phase 2 trial sought to evaluate the efficacy and safety of the combination of anlotinib and sintilimab in patients with recurrent advanced endometrial cancer.

The study enrolled 23 patients from November 2019 to September 2020. To be eligible for enrollment, females aged 18 and older must have received at least 1 platinum-based chemotherapy, have at least 1 measurable lesion according to the Response Evaluation Criteria in Solid Tumors, and have an ECOG performance status of 0 or 1. All 23 patients were evaluable.²

Patients with FIGO stage IA (21.7%), IB (8.7%), II (4.4%), IIIA (13.1%), IIIC (30.4%), IVB (21.7%) were also included within the trial.

Anlotinib was administered orally at 12 mg a day from days 1-14 in each 21-day cycle in addition to sintilimab administered intravenously on day 1 of each 21-day cycle.

Objective response rate (ORR) was the primary end point with some secondary end points including disease control rate (DCR), progression free survival (PFS), and overall safety (OS).

Results from the therapeutic evaluation showed that the incidence of complete response, partial response, stable disease (SD) and progression disease was 17.4%, 56.5%, 17.4% and 8.7% respectively, yielding the ORR of 73.9% (95%CI, 51.6%-89.8%) and a DCR of 91.3% (95%CI, 72.0%-98.9%). Additionally, 12.8 months was the median PFS (95%Cl, 4.8 to not reached).

In 22 evaluable patients, responses were ongoing in 8 patients at the time of data cutoff. Notably, the duration of response reached 16 months in 1 patient and the shortest time to response was under 2 months.Compared with baseline measurements, 3 patients in the study had residual lymph nodes < 10 mm following treatment with anlotinib plus sintilimab, while 1 patient had immune-related SD and 1 experienced progression of non-target lesions.

The median time of the first response was 1.5 months (range, 0.7-12.8). The median PFS was not reached.

Though adverse events (AEs) occurred in greater than 10% of patients during the study, most were grade 1 or 2. The most common any-grade AEs were hand-foot syndrome (60.9%), lymphocytopenia (43.5%) and fatigue (43.5%). Grade 3 or 4 AEs included erythra (13.0%), lymphocytopenia (8.7%), hand-foot syndrome (8.7%), ileus (4.3%), immune myocarditis (4.3%), immune peritonitis (4.3%), hypertension (4.3%), and fatigue (4.3%). No unexpected safety signals or treatment-related deaths occurred throughout the study. No unexpected safety signals or treatment-related deaths occurred throughout the study.

More data are expected to come with results from future studies.

REFERENCES:

1. Wei W, Ban X, Yang F et al. Anlotinib plus sintilimab in patients with recurrent advanced endometrial cancer: A prospective open-label, single-arm, phase II clinical trial. Presented at: American Society of Clinical Oncology 2021; Abstract 5583

2. Anti-PD-1 Antibody Combined With Anlotinib in the Treatment of Endometrial Cancer. ClinicalTrials.gov. Accessed February 15, 2022. https://bit.ly/3BqKiFE