Cabozantinib efficacy extends to non-clear-cell RCC
medwireNews: Almost three-quarters of patients with non-clear-cell renal cell carcinoma (RCC) may benefit from treatment with the tyrosine kinase receptor inhibitor cabozantinib, suggesting its efficacy is not limited to clear-cell disease, say researchers.
“In the absence of prospective data, this study provides support for the use of cabozantinib in real-world clinical practice in patients with non-clear-cell renal cell carcinoma, for whom effective treatment options are few and a standard second-line therapy is absent,” Lauren Harshman (Harvard Medical School, Boston, Massachusetts, USA) and co-authors write in The Lancet Oncology.
Their retrospective study, using data from 22 centers in the USA and Belgium, included 112 patients (median age 60 years, 76% men) with metastatic non-clear-cell RCC who received oral cabozantinib during any treatment line given between 2015 and 2018.
Of these, 59% had tumors with papillary histology, 15% had Xp11.2 translocation histology, 13% had unclassified histology, 9% had chromophobe histology, and 4% had collecting duct histology.
During a median follow-up of 11.0 months, 27% of patients achieved an objective response (complete or partial response) overall, with the rate ranging from 13% among patients with unclassified histology to 50% among those with collecting duct histology. In the same two histologic groups, the clinical benefit rate (objective response or stable disease) was 67% and 100%, respectively, with 74% of patients achieving clinical benefit overall.
The researchers note that the objective response rate was similar between patients who received first-line cabozantinib compared with those who received it as a later-line treatment (23 vs 28%) and also occurred irrespective of CDKN2A or MET mutation status.
Treatment failure occurred after a median 6.7 months, while median progression-free and overall survival times were 7.0 and 12.0 months, respectively.
The toxicity profile was as expected, note the investigators, and there were no treatment-related deaths.
Harshman and team comment that, despite nearly a quarter of patients “having had three or more previous systemic therapies and 89% having poor-risk or intermediate-risk disease, […] robust clinical activity, comparable to that seen in the pivotal trials of cabozantinib in clear-cell disease, was observed across all non-clear-cell subtypes and lines of treatment, which might reflect the broad biological activity of cabozantinib in antagonising multiple oncogenic pathways.”
They add that “[t]hese results suggest that the antitumour activity of cabozantinib is not restricted to clear-cell histology.”
The authors conclude that their study highlights “the crucial need to support prospective clinical trials and international collaborations to improve outcomes in these rare and heterogeneous group of diseases amassed under the umbrella term non-clear-cell renal cell carcinoma.”
In an accompanying commentary, Paul Russo, from Memorial Sloan Kettering Cancer Center in New York, USA says that “this study provides clinicians with credible information that can guide treatment of these notoriously difficult tumours.”
He adds: “Because of the rarity of these tumours, large-scale prospective trials that are successful in metastatic clear-cell renal cell carcinoma will be difficult, if not impossible, to do. Yet, the determination of a such a large group of oncologists to provide real-world care to their patients while obtaining and analysing these data is truly remarkable.”
By Laura Cowen
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