The potential use of RNA sequencing to improve treatment selection in advanced RCC

Tian Zhang, MD, MHS, associate professor, the Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses RNA sequencing to identify biologic cluster assignment could improve first-line treatment selection in metastatic renal cell carcinoma (RCC).

The array of available targeted treatment options in advanced RCC necessitates improved guidance when determining a patient’s optimal treatment approach, Zhang begins. It was hypothesized that identifying biologic drivers of RCC in a given tumor would allow for better prediction of patient benefit with standard-of-care immunotherapy regimens, thereby improving outcomes.

The phase 2 OPTIC RCC trial (NCT05361720) was designed to test this hypothesis by prospectively evaluating gene expression in tissue samples from patients with newly diagnosed, metastatic clear cell RCC. It is the first prospectively, molecularly-selected trial in RCC, and is supported by data from several correlative studies in large 3 studies, Zhang states.

Using RNA sequencing, tumors will be assigned to 1 of 7 genomic/transcriptomic clusters identified in the phase 3 IMmotion151 trial (NCT02420821), Zhang continues. Correlative analyses of IMmotion151 demonstrated that these clusters were driven by either angiogenic or immune-related gene expression and were more responsive to VEGF targeted therapy and immunotherapy, respectively, Zhang explains.

Accordingly, cabozantinib (Cabometyx) and nivolumab (Opdivo) will be administered to patients with angiogenic signatures, whereas ipilimumab (Yervoy) and nivolumab will be administered to patients with immune-inflammatory signatures, Zhang states.

The primary end point of OPTIC RCC is objective response rate (ORR) according to RECIST v1.1 criteria. Positive signals for efficacy and clinical outcomes from the trial would indicate the utility and accuracy of molecular signature identification as a tool for prospective treatment selection in advanced RCC, Zhang says.


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