Comprehensive Genomic Profiling of Metastatic Tumors in a Phase 2 Biomarker Study of Everolimus in Advanced Renal Cell Carcinoma

Clinical Genitourinary Cancer
Xin GaoRupal S Bhatt

Abstract

Genomic events leading to activation of mechanistic target of rapamycin (mTOR) are common in renal cell carcinoma (RCC). Everolimus is an allosteric mTOR inhibitor with efficacy in metastatic RCC. We characterized the genomic profile of RCC tumors from metastatic sites and assessed whether particular alterations correlate with clinical response to everolimus. An open-label, single-arm phase 2 biomarker study of everolimus 10 mg daily was conducted in metastatic RCC patients. Needle biopsy or metastasectomy was performed on metastatic tumors before everolimus initiation. Next-generation sequencing was performed using a targeted hybrid capture panel detecting alterations within exons and key introns of ≥ 300 cancer-associated genes. Disease assessments were obtained every 8 weeks using standard radiographic modalities and evaluated by Response Evaluation Criteria in Solid Tumors criteria. Objective response was seen in 1 (4.2%) of 24 patients. Two patients (8.3%) had stable disease lasting > 6 months. Median (90% confidence interval) overall and progression-free survival were 20.1 (8.6, NA) and 3.8 (2.4, 5.4) months, respectively. Next-generation sequencing was successful on 18 pretreatment specimens and 3 on-treatment specimens....Continue Reading

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