medwireNews: A meaningful proportion of patients with advanced renal cell carcinoma (RCC) with variant histology or sarcomatoid differentiation respond to the immunotherapy combination of atezolizumab and bevacizumab without experiencing severe toxicity, phase II study data show.
“The combination demonstrated responses across several subtypes of RCC, including collecting duct and medullary carcinoma, histologies that are often treated with cytotoxic chemotherapy,” write Toni Choueiri (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and co-authors in the Journal of Clinical Oncology.
They add: “This is notable given the generally poor prognosis and low response rates associated with variant histology RCC in trials to date.”
The trial included 60 patients with advanced RCC with variant histology (n=42) or clear cell RCC with at least 20% sarcomatoid differentiation (n=18) who received atezolizumab 1200 mg and bevacizumab 15 mg/kg intravenously every 3 weeks. The majority (65%) of patients had not previously been treated.
After a median 13.0 months of follow-up, the objective response rate (ORR) for the overall population was 33%, with responses occurring after a median 2.7 months and lasting for a median of 8.9 months.
The ORR was higher among the patients with clear cell RCC with sarcomatoid differentiation than among those with variant histology RCC, at 50% and 26%, respectively.
In addition, PD-L1-positive (≥1% expression on tumor cells) patients (n=15) were more likely to respond to treatment than PD-L1-negative patients (n=25), with ORRs of 60% and 19%, respectively, overall. The corresponding rates among patients with clear cell RCC with sarcomatoid differentiation were 50% and 29%, while patients with variant histology RCC had ORRs of 67% and 14% when PD-L1-positive and negative, respectively.
Median progression-free survival overall was 8.3 months, and median overall survival had not been reached at the time of the analysis.
One third of patients experienced at least one treatment-related grade 3 adverse event. There were no treatment-related grade 4 or 5 toxicities, however. Five (8.3%) patients discontinued treatment due to unacceptable toxicity.
Choueiri et al say their findings highlight “the need for ongoing clinical trials to evaluate immune checkpoint inhibitor combinations in this diverse patient population given the unmet clinical need to improve outcomes for patients with variant histology RCC.”
They add that, although a confirmatory randomized trial is needed, “the current study provides support for the use of immunotherapy/[vascular endothelial growth factor] combinations in the management of variant histology RCC and RCC with sarcomatoid differentiation.”
Earlier findings from the trial were presented at the 2019 ASCO Genitourinary Cancers Symposium in San Francisco, California, USA and reported by medwireNews.
By Laura Cowen
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