(UroToday.com) Dr. Bradley McGregor presents the results of a phase II study of cabozantinib (Cabo) with nivolumab (Nivo) and ipilimumab (Ipi) in advanced renal cell carcinoma with variant histologies (RCCvh).
As Dr. McGregor and team note, renal cell carcinoma with variant Histology (RCCvh) or non-clear cell RCC is a heterogeneous group of diseases with a worse prognosis than clear cell RCC. In Cosmic-313,1 triplet therapy of cabozantinib (Cabo) with Nivolumab (Nivo)/Ipilimumab (Ipi) improved progression free survival over Nivo/Ipi alone in patients with clear cell renal cell carcinoma, but the survival data remains immature. it should be noted that there were significant toxicity with 73% of patients experiencing grade three or four adverse events and only 58% of patients receiving all four doses of IPI.
At this time combinations of immunotherapy and targeted therapy yield response rates near 50% in patients with RCCvh, but novel approaches are still needed. The authors of this trial expanded the treatment paradigm of the Cosmic-313 study to patients with variant Histology RCC.
The study schema is seen below:
Eligible patients may have received one line of prior therapy excluding immunotherapy.
To-date, 39 patients have been enrolled.
Demographics below:
Looking at treatment exposure in these 39 patients, 44% received all four doses of Nevada and EPI while 34% receive two doses or less. 72% of patients had a dose reduction in cabozantinib to 20 milligrams daily and the remaining 18% were reduced to 20 milligrams every other day.
There was good tumor response as seen below:
An objective response was seen in eight patients which results in an objective response rate of 21%. ORR broken down below:
ORR was best in papillary RCC and less in chromophobe RCC.
Looking at PFS and OS:
Median progression-free survival was 8.9 (95% CI, 4.2-12.7) months.
Unfortunately, as noted by the dose reductions, TRAEs were high. 74% developed treatment-related grade 3 or higher toxicities. This included 37% (n=14) developed ≥ grade 3 elevation in AST or ALT. 29% (n=11) required high dose steroids (prednisone ≥ 40 mg daily or equivalent).
No grade 5 toxicity has been reported.
Based on this, the authors conclude that this triplet therapy appears to have clinically meaningful activity in a subset of patients with variant Histology RCC. however, I would note that with significant dose reduction and a large proportion of patients having adverse effects, the benefit may be limited by the toxicity and ability to receive the full dose of therapy.
They have opened an expansion cohort of patients with a lower dose of cabozantinib (20 mg) and perhaps that might be better tolerated.Presented by: Bradley Alexander McGregor, MD, Director of Clinical Research, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA
Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Associate Professor of Urology, University of California, Davis, @tchandra_uromd @UCDavisUrology on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.
References:
- Choueiri TK, Powles T, Albiges L, Burotto M, Szczylik C, Zurawski B, Yanez Ruiz E, Maruzzo M, Suarez Zaizar A, Fein LE, Schutz FA, Heng DYC, Wang F, Mataveli F, Chang YL, van Kooten Losio M, Suarez C, Motzer RJ; COSMIC-313 Investigators. Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. N Engl J Med. 2023 May 11;388(19):1767-1778. doi: 10.1056/NEJMoa2212851. PMID: 37163623.