(UroToday.com) The 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between January 25th and 27th was host to a renal cell, adrenal, and testicular cancers rapid oral abstract session. Dr. Enrique Grande presented the results of a multi-cohort basket phase II trial, CABATEN/GETNE-T1914 evaluating cabozantinib plus atezolizumab in patients with locally advanced/metastatic adrenocortical carcinoma.
Dr. Grande noted that adrenocortical carcinoma is a rare endocrine malignancy with an estimated incidence of 0.5 – 2 new cases per million people annually.1 Mitotane, an adrenolytic agent, remains, since 1970, the only Food and Drug Administration (FDA)-approved drug for adrenocortical carcinoma.2 Treatment options for patients with disease progression following mitotane and platinum-based chemotherapy combination options remain limited, and the 5-year overall survival for such patients with advanced disease is <15%.3 Immune-checkpoint inhibitors (ICIs) and targeted therapies have shown limited activity as single agents for patients with advanced/metastatic adrenocortical carcinoma.4-6 As such, the CABATEN trial aimed to assess the efficacy and safety of the combination of cabozantinib plus atezolizumab across the spectrum of different endocrine neoplasms, including a cohort of patients with advanced/metastatic adrenocortical carcinoma.
CABATEN is an academic, prospective, multicenter, phase II single arm basket trial that recruited patients with neuroendocrine and endocrine neoplasms across six cohorts. The adrenocortical carcinoma cohort included patients with disease progression following chemotherapy and/or mitotane with no prior exposure to any tyrosine kinase inhibitors (TKIs) or ICIs and ECOG performance status of 0 – 1. There were no limits as to the number of prior lines of treatment.
Patients received atezolizumab 1,200 mg IV every 3 weeks plus cabozantinib 40 mg/day orally. The primary study objective was the objective response rate (ORR). Secondary objectives included:
- Progression-free survival (PFS)
- Overall survival (OS)
- Safety
- Duration of response
- Biomarker analysis
This trial followed Simon’s II optimal two-stage design as follows:
The adrenocortical carcinoma cohort included 24 patients with baseline characteristics summarized below. The median age was 51 years and the majority had stage IV disease at diagnosis (88%) and ≥2 sites of metastasis, with the liver (63%) and lungs (54%) as the most common sites of disease spread. Consistent with the eligibility criteria, all patients had received prior systemic therapy (1: 46% ; ≥2: 54%), most commonly with chemotherapy (92%).
For the primary outcome of ORR, only 2/26 patients (8.3%) achieved an ORR. The disease control rate 33.3%, with a median duration of response of 11.4 months.
At a median follow-up of 10.7 months (range: 4.6 – 16.2), the median PFS was 2.9 months (95% CI: 2.8 – 5.7) and the median OS was 13.5 months (95% CI: 8.8 – not reached).
The median duration of treatment was 3.0 and 3.4 months for cabozantinib and atezolizumab, respectively. Due to adverse events, cabozantinib and atezolizumab treatment was temporarily interrupted in 46% and 25% of patients, respectively. The most common adverse events were consistent with the drugs’ known toxicity profiles:
Dr. Grande concluded as follows:
- The combination of cabozantinib plus atezolizumab has limited activity in refractory advanced/metastatic adrenocortical carcinoma
- The safety profile of a combination cabozantinib plus atezolizumab was consistent with that from previous reports
- There were patients with long-lasting responses, thus meriting further investigation into predictive factors that may help select those who may benefit most from this combination
Presented by: Enrique Grande, MD, PhD, MSc, Director of the Medical Oncology Program and Clinical Research lead, Medical Oncology Department, MD Anderson Cancer Center Madrid, Madrid, Spain
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, January 25th – January 27th, 2024
References:- Fassnacht M, Assie G, Baudin E, et al. Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(11):1476-90.
- Netto AD, Wajchenberg BL, Ravaglia C, et al. TREATMENT OF ADRENOCORTICAL CANCER WITH O,P'-DDD. Ann Intern Med. 1963;59:74-8.
- Sharma E, Dahal S, Sharma P, et al. The Characteristics and Trends in Adrenocortical Carcinoma: A United States Population Based Study. J Clin Med Res. 2018;10(8):636-40.
- Nitya R, Zheng Y, Kelly V, et al. PD-1 Blockade in Advanced Adrenocortical Carcinoma. J Clin Oncol. 2020;38(1):71-80.
- Kroiss M, Quinkler M, Johanssen S, et al. Sunitinib in refractory adrenocortical carcinoma: a phase II, single-arm, open-label trial. J Clin Endocrinol Metab. 2012;97(10):3495-503.
- O’Sullivan C, Edgerly M, Velarde M, et al. The VEGF inhibitor axitinib has limited effectiveness as a therapy for adrenocortical cancer. J Clin Endocrinol Metab. 2014;99(4):1291-7.