(UroToday.com) The European Society of Medical Oncology (ESMO) 2021 annual meeting’s non-prostate cancer mini-oral session included a presentation by Dr. Giuseppe Procopio discussing results from the phase 2 BONSAI trial.
Metastatic collecting duct carcinoma is biologically poorly characterized and under-represented in prospective randomized trials. At the ESMO congress, Dr. Procopio and colleagues presented results of BONSAI, a prospective, phase 2 trial of frontline cabozantinib in metastatic collecting duct renal cell carcinoma.
BONSAI tested cabozantinib 60 mg in treatment-naïve metastatic collecting duct carcinoma patients. The primary endpoint for the trial was objective response rate (ORR) per RECIST 1.1. Secondary endpoints were progression-free survival (PFS), overall survival, and safety profile. Exploratory objectives were to identify somatic mutations by targeted DNA sequencing and to define molecular subtypes, signatures, and transcript fusions genes by RNA sequencing. A central pathological review was mandatory and the study was based on Simon’s two-stage optimal design. The trial design for BONSAI is as follows:
From January 2018 to November 2020, 25 patients were enrolled, of whom 23 started treatment. The median age was 66 years and 83% of patients were male. The most common metastatic sites were lymph nodes and bone (15 and 13 patients, respectively), followed by lung and liver (10 and 4 patients, respectively). The median follow-up time was 8 months over which the median PFS was 6 months. ORR was 35% (1 complete response and 7 partial responses), with a summary of the tumor response as follows:
All patients reported at least one grade 1-2 adverse events: the most common were fatigue (43%), hypothyroidism (28%), stomatitis (28%), anorexia (26%), hand-foot syndrome (13%), hypertension (17%), and diarrhea (13%). Five patients reported grade 3 adverse events (2 thromboembolic events, 2 arterial hypertension, and 1 fatigue), while no grade 4-5 adverse events were reported. Among treated patients, 17% of patients required dose reduction. DNA sequencing was successful in 21 (91%) patients and all tumors were microsatellite stable. No association between tumor mutational burden and response to cabozantinib was observed. The most affected pathways were chromatin-modifying enzymes (46%) and adaptive immune system (23%). Responsive patients (PFS > 6 months) showed a high frequency of mutations affecting deubiquitination, cell-cell communication, and TGF-b signaling. Non-responders were frequently mutated in chromatin remodeling, transcriptional regulation, and WNT pathways.
- The study met its primary endpoint showing promising efficacy and acceptable tolerability of cabozantinib in metastatic collecting duct carcinoma patients
- The evaluation of molecular profiling performed during treatment is ongoing in order to assess the modulating activity of cabozantinib on local and systemic tumor immunity
Presented by: Giuseppe Procopio, MD, Medical Oncology Dept., Director of the Genitourinary Cancer Unit at The National Cancer Institute Foundation, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Society for Medical Oncology (ESMO) Annual Congress 2021, Thursday, Sep 16, 2021 – Tuesday, Sep 21, 2021.