Anlotinib for the treatment of locally advanced or metastatic pheochromocytoma and paraganglioma: A retrospective study.

Abstract

e16209 Background: Pheochromocytomas (PCC) and paragangliomas (PGL) are rare hyper-vascular neuroendocrine tumors derived from the adrenal medulla and paraganglia, respectively. In previous studies, the overall survival at 5 years for patients (pts) with metastatic disease was only 50% to 60% after the diagnosis of metastases. Anlotinib is a novel multikinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. This study investigated the efficacy and safety of anlotinib monotherapy or in combination with other therapies in treating locally advanced or metastatic (LA/M) PCC and PGL. Methods: Pts with histologically or cytologically confirmed unresectable or progressive LA/M PCC or LA/M PGL were enrolled from March 2020 to October 2021. The inclusion criteria contained: (a) age 18 or older, (b) ECOG performance status 0–2, (c) adequate organ and marrow function. Eligible pts received anlotinib monotherapy or in combination with peptide receptor radionuclide therapy (PRRT) or 131I-MIBG. Anotinib was given orally 12 mg once daily (d1-d14, q3w) until the disease progression or the intolerable toxicities. Tumor response was assessed according to RECIST1.1. Results: 35 pts were enrolled (Table) and 25 were assessed for tumor response. Among them, 17 received anlotinib alone, others were treated with the combination regimen, including 6 with PRRT, and 2 with 131I-MIBG respectively. At the data cut-off date on January 15th, 2022, 4 pts progressed and 1 died. The median duration of treatment was 8.5 months. 10 pts (40%) achieved partial response (PR) and the stable disease (SD) was observed in 13 pts (52%). The objective response rate (ORR) for 25 pts was 40% and the disease control rate (DCR) was 92%. For pts with PCC and PGL, the ORR was 33.3% and 46.2%, respectively. All pts were assessed for safety. The most common adverse events (AEs) included: malaise (23 pts, 65.7%), palmar-plantar erythrodysesthesia syndrome (PPE) (23 pts, 65.7%), hypertension (22 pts, 62.9%) and oropharyngeal pain (17 pts, 48.6%). The most common grade 3 or worse AEs were hypertension (15 pts) and PPE (4 pts), which were claimed tolerable by the pts. Conclusions: This single-center retrospective study indicated that anlotinib monotherapy or in combination with radionuclide therapy showed promising efficacy and favourable safety profile in the treatment of LA/M PCC and PGL, which is worthy of further exploration.[Table: see text]