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Genomic Alterations and Outcomes in Patients With Renal Cancer Receiving Everolimus

By: Sarah Campen, PharmD
Posted: Monday, November 12, 2018

Despite previous retrospective reports that highlighted “unusual” benefit from rapalog agents in patients with advanced renal cell carcinoma in the presence of acquired mutations in PI3K pathway components, a new analysis has found no significant association between therapeutic benefit and mutation status for PI3K pathway components, including TSC1, TSC2, and mTOR. The study was published in Clinical Cancer Research.

However, an immunohistochemistry analysis did reveal a significant correlation between loss of PTEN expression and favorable progression-free survival for everolimus. “These findings suggest that the PTEN expression status may have a clinically meaningful predictive value, and a putative biomarker, which warrants further investigation in independent [renal cell carcinoma] cohorts,” stated corresponding author Martin H. Voss, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues.

The researchers analyzed specimens from 184 everolimus-treated patients with renal cell carcinoma. The samples, collected at baseline in the RECORD-3 study, were evaluated using targeted next-generation sequencing. Mutation rates in genes of interest were 6% (TSC1), 4.4% (TSC2), and 8.2% (mTOR); 44% of these genes harbored alterations in at least one PI3K pathway component.

Regardless of the absence or presence of mutations in TSC1, TSC2, or mTOR, progression-free survival did not differ. Patients treated with everolimus with retained (n = 50) versus lost (n = 50) PTEN immunohistochemistry expression had a median progression-free survival of 5.3 months and 10.5 months, respectively (P < .001). This association was not observed, however, with sunitinib.

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