Anlotinib in patients with recurrent platinum-resistant or platinum-refractory ovarian carcinoma: A prospective, single-center, single-arm, phase II clinical trial (033)

Abstract

Objectives: Patients with platinum-resistant recurrent ovarian cancer lack effective treatment. This phase II study (ChiCTR2000029654) was conducted to evaluate the efficacy and safety of anlotinib, a new multi-tyrosine kinase inhibitor (TKI) for tumor angiogenesis and proliferative signaling, monotherapy in patients with platinum-resistant or refractory ovarian carcinoma (OC). We presented the updated progression-free survival (PFS), objective response rate (ORR), and safety data in more patients. Methods: Patients who had histologically confirmed high-grade serous gonadal ovarian cancer (including salpingo carcinoma and peritoneal carcinoma), had experienced disease progression during or within six months of discontinuation, received at least two lines of platinum-based chemotherapy, or previously received second-line or more chemotherapy, were eligible for the study. No prior targeted therapy and intraperitoneal radiotherapy, and ECOG PS 0-2 were required for enrollment. Patients had at least one lesion (measurable and/or nonmeasurable) that could be accurately assessed at baseline by computed tomography/magnetic resonance imaging. Patients received anlotinib 12mg orally once daily (d1-14; 21 days per cycle) until disease progression, death, unacceptable toxicity, or consent withdrawal. Therapeutic effects were evaluated every six weeks. The primary endpoint was ORR and the secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) by RECIST 1.1. Results: From March 2019 to April 2021, 31 patients (female) with a median age of 59 years (range: 39-73), FIGO histopathological stage IC (1, 3.5%), IIC (2, 6.9%), IIIC (20, 69.0%) and IV (6, 20.7%) were enrolled. Twenty-seven of these patients were evaluable. In the efficacy-evaluable population (n=27), the therapeutic evaluation showed that complete response, partial response, stable disease, and progressive disease was 3.7%, 22.22%, 40.74%, and 33.33%, respectively, yielding the ORR of 25.9% (7/27; 95% CI: 11.1-46.3).The DCR was 66.7% (18/27; 95% CI: 46.0-83.5). The median PFS was 5.32 months (95% CI: 4.31-6.33). The median OS was not reached. The most common adverse events (AEs) were grade 1 or 2, which included hypertension (41.94%), fatigue (22.58%), hand-foot syndrome (29.03%), gingival bleeding (4.76%), hand-foot syndrome (4.76%), renal dysfunction (4.76%) and cancer pain (4.76%). The grade 3 AEs only included myocardial infarction (4.76%) and urine occult blood (4.76%). No higher AEs and treatment-related death were observed. Conclusions: Anlotinib showed an encouraging antitumor activity for patients with recurrent platinum-resistant or refractory ovarian carcinoma. Adverse events were consistent with the established safety profiles of anlotinib. We will report more data in the future. Objectives: Patients with platinum-resistant recurrent ovarian cancer lack effective treatment. This phase II study (ChiCTR2000029654) was conducted to evaluate the efficacy and safety of anlotinib, a new multi-tyrosine kinase inhibitor (TKI) for tumor angiogenesis and proliferative signaling, monotherapy in patients with platinum-resistant or refractory ovarian carcinoma (OC). We presented the updated progression-free survival (PFS), objective response rate (ORR), and safety data in more patients. Methods: Patients who had histologically confirmed high-grade serous gonadal ovarian cancer (including salpingo carcinoma and peritoneal carcinoma), had experienced disease progression during or within six months of discontinuation, received at least two lines of platinum-based chemotherapy, or previously received second-line or more chemotherapy, were eligible for the study. No prior targeted therapy and intraperitoneal radiotherapy, and ECOG PS 0-2 were required for enrollment. Patients had at least one lesion (measurable and/or nonmeasurable) that could be accurately assessed at baseline by computed tomography/magnetic resonance imaging. Patients received anlotinib 12mg orally once daily (d1-14; 21 days per cycle) until disease progression, death, unacceptable toxicity, or consent withdrawal. Therapeutic effects were evaluated every six weeks. The primary endpoint was ORR and the secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) by RECIST 1.1. Results: From March 2019 to April 2021, 31 patients (female) with a median age of 59 years (range: 39-73), FIGO histopathological stage IC (1, 3.5%), IIC (2, 6.9%), IIIC (20, 69.0%) and IV (6, 20.7%) were enrolled. Twenty-seven of these patients were evaluable. In the efficacy-evaluable population (n=27), the therapeutic evaluation showed that complete response, partial response, stable disease, and progressive disease was 3.7%, 22.22%, 40.74%, and 33.33%, respectively, yielding the ORR of 25.9% (7/27; 95% CI: 11.1-46.3).The DCR was 66.7% (18/27; 95% CI: 46.0-83.5). The median PFS was 5.32 months (95% CI: 4.31-6.33). The median OS was not reached. The most common adverse events (AEs) were grade 1 or 2, which included hypertension (41.94%), fatigue (22.58%), hand-foot syndrome (29.03%), gingival bleeding (4.76%), hand-foot syndrome (4.76%), renal dysfunction (4.76%) and cancer pain (4.76%). The grade 3 AEs only included myocardial infarction (4.76%) and urine occult blood (4.76%). No higher AEs and treatment-related death were observed. Conclusions: Anlotinib showed an encouraging antitumor activity for patients with recurrent platinum-resistant or refractory ovarian carcinoma. Adverse events were consistent with the established safety profiles of anlotinib. We will report more data in the future.