Lenvatinib as a Therapeutic Option in Unresectable Metastatic Pheochromocytoma and Paragangliomas

Lauren Hassan Nelson; Harry Fuentes-Bayne; Jun Yin; Erik Asmus; Mabel Ryder; John C. Morris; Crystal R. Hilger; Keith C. Bible; Ashish V. Chintakuntlawar; Sarika N. Rao


J Endo Soc. 2022;6(5) 

In This Article


Study Objectives

Metastatic PPGL is defined as the presence of chromaffin cells where these cells should not exist, or invasion of the PPGL into local tissue.[24] The primary objective was to determine the overall response rate (ORR), defined as the percentage of patients who had a partial response (PR) or complete response to lenvatinib in patients with mPPGL. Secondary objectives were to determine overall survival (OS), progression-free survival (PFS), and duration of response.

Study Design and Participants

This was initially a phase 2 prospective study (NCT03008369) analyzing patients who received lenvatinib for mPPGL. However, due to slow accrual rate, the trial was terminated. Hence, the non-trial patients treated with lenvatinib were reviewed retrospectively. This study was approved by the Mayo Clinic Institutional Review Board. We searched our hospital medical records from 2015 to 2020 to identify patients with mPPGL treated with lenvatinib. Patients with confirmed mPPGL were included if they met the following criteria: ≥ 18 years of age, disease not amenable to localized treatments, Eastern Cooperative Oncology Group (ECOG) performance status < 2, life expectancy > 24 weeks, normal liver and kidney function, and well-controlled blood pressure.

Exclusion criteria included: additional unrelated primary malignancy within the past 2 years, other PPGL treatment modalities ≤ 21 days prior to start of drug, poor tolerance to other treatments, advanced or untreated cardiovascular disease, known active and/or untreated brain metastases, prior use of lenvatinib, high risk for gastrointestinal perforation, ongoing treatment of thrombotic event, active infection, pregnant or nursing women, and men or women of childbearing potential who were unwilling to use contraception.

Patients in the prospective study were eligible only if they had measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.[6] Other non-trial patients could have nonmeasurable disease such as bone metastasis, pleural effusion, or lymph nodes < 1.5 cm.

Patients were started on lenvatinib 20 mg daily, the dose was adjusted based on the criteria outlined in the protocol. Dose was held or reduced based on degree of adverse events, generally if grade ≥ 2 or 3. Cycle of treatment was defined as every 28 days. Parameters collected included baseline demographics, germline or somatic mutational status (screening for SDHx, RET, VHL, NF1), previous treatment modalities (ie, surgery, chemotherapy, radiotherapy, 131I-MIBG, or MKI), number of completed cycles, hormonal response. The adverse events (AEs) were graded based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.

Statistical Analysis

Patient demographic information was summarized using descriptive analysis. Response to lenvatinib was based off of RECIST 1.1 criteria. Kaplan-Meier curves were used to assess OS, PFS, and treatment duration. OS was defined as length of time patients remained alive after starting lenvatinib. PFS was defined as length of time from drug initiation until date of first disease progression or death. SAS version 9.4 software was used to calculate the statistical data.