Cabozantinib as First-line Treatment in Patients With Metastatic Collecting Duct Renal Cell Carcinoma: Results of the BONSAI Trial for the Italian Network for Research in Urologic-Oncology (Meet-URO 2 Study)

Abstract

Importance: Metastatic collecting duct carcinoma (mCDC) is a rare type of non-clear cell renal cell carcinoma (ncRCC) with poor prognosis and no standard treatments. Despite retrospective series that have documented the benefit of cabozantinib in ncRCC, no prospective trials have evaluated this treatment in mCDC.

Objective: To determine whether cabozantinib is an active treatment in patients with mCDC.

Design, setting, and participants: The caBozantinib in cOllectiNg ductS Renal Cell cArcInoma (BONSAI) trial was an open-label, single-arm, phase 2 clinical trial carried out between January 2018 and November 2020 at a single academic center with data cut off in September 2021 on behalf of the the Italian Network for Research in Urologic-Oncology (Meet-URO 2). Eligible patients had histologic diagnosis of centrally confirmed mCDC with measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). In total, 25 patients were screened.

Interventions: Patients received cabozantinib, 60 mg orally once daily, until disease progression, unacceptable toxic effects, or withdrawal of consent.

Main outcomes and measures: The primary end point was objective response rate (ORR) per RECIST, version 1.1.

Results: At data cut off, of 25 patients enrolled, 23 started treatment because 2 were excluded after failing the screening process at pathologic review. The median follow-up cannot be estimated using the reverse Kaplan-Meier estimator. The median time to censoring was 11 months (95% CI, 0-22 months). Median (range) age was 66 (53-74) years. As best overall response, 3 patients presented stable disease, 1 patient achieved a complete response, and 7 a partial response. The ORR was 35% (95% CI, 16%-57%). The median progression-free survival was 4 months (95% CI, 3-13 months). The median OS was 7 months (95% CI, 3-31 months). All patients reported at least 1 grade (G) 1 to 2 adverse event (AE). The most common G1 to G2 AEs were fatigue (14 [60%]), anorexia (9 [39%]), hand-foot syndrome (7 [30%]), hypothyroidism (7 [30%]), mucositis (7 [30%]), diarrhea (5 [22%]), and hypertension (3 [13%]). Six G3 AEs were reported: 2 arterial hyperthension, 1 pulmonary thromboembolism, 1 bleeding, and 2 fatigue. There were no permanent discontinuations from the study owing to AEs. Four patients (17%) required dose reduction to 40 mg, and 4 (17%) required a transitory interruption to manage toxic effects.

Conclusions and relevance: The study met the ORR primary end point, showing encouraging efficacy of cabozantinib in untreated patients with mCDC. Further investigations to advance the molecular understanding of this tumor are ongoing.

Trial registration: ClinicalTrials.gov Identifier: NCT03354884.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Procopio reported funding from Ipsen during the conduct of the study; personal fees from AstraZeneca, Bayer, BMS, Ipsen, Janssen, MSD, Novartis, Pfizer, and Eisai outside the submitted work. Dr Sepe reported funding from Ipsen during the conduct of the study. Dr Giannatempo reported personal fees from Merck and Janssen, grants from AstraZeneca, and Ipsen outside the submitted work. Dr de Braud reported personal fees (honoraria) from ROCHE, EMD Serono, NMS Nerviano Medical Science, Sanofi, MSD, Novartis, Incyte, BMS, Menarini, Merck Group, Pfizer, Servier, Amgen, Dephaforum, and Pharmadoc outside the submitted work. Dr Verzoni reported personal fees from Ipsen during the conduct of the study; personal fees from Janssen, Ipsen, MSD, Pfizer, Merck, and Novartis outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Patient Disposition

Figure 2.. Kaplan-Meier Curves

A, Progression-free survival (PFS). B, Overall survival (OS).