No genomic biomarkers of PFS-2 for RCC patients on immunotherapy-based combination therapies
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Key takeaways:
- Researchers did not identify a discrete genomic biomarker to guide first-line regimen selection in patients with advanced clear cell RCC.
- Clinical stratification remains key for regimen selection.
CHICAGO — Researchers were unable to identify a discrete genomic biomarker of PFS after second line of therapy to help guide first-line regimen selection for patients with advanced clear cell renal cell carcinoma, according to a poster presentation at ASCO Annual Meeting.
“Currently, first-line regimen selection is done based on a clinical stratification system whereby various clinical factors are taken into account and there is no clear discrete biomarker that is either predictive or prognostic for any specific first-line treatment regimen,” Kelly N. Fitzgerald, MD, a medical oncology fellow at Memorial Sloan Kettering Cancer Center, said in the presentation.
PFS-2, defined as the time from the start of first line therapy until progression on next therapy or death, is a superior surrogate for OS as compared with PFS, according to Fitzgerald.
In this single-institution retrospective study, researchers examined the impact of individual mutations on PFS-2 in 141 patients who had clear cell RCC and received first-line immunotherapy-based combination therapies at Memorial Sloan Kettering Cancer Center between 2014 and 2020. First-line treatments included ipilimumab with nivolumab (IO/IO) and tyrosine kinase inhibitors targeting vascular endothelial growth factor receptor (TKI/IO).
A log-rank test and model-based approach was used to assess the PFS-2 association with each mutation, and an interaction test between somatic mutation and treatment group was used to test for heterogeneity of effect among treatment groups.
The most common somatic mutations included VHL, mTOR pathway, PBRM1, BAP1 and TP53, but only BAP1 was significantly associated with PFS-2. The median PFS-2 was 17 months for patients with BAP1 mutation and 44 months for those without. No significant variation occurred in the treatment effect of IO/IO or tyrosine kinase inhibitor/IO based on the presence or absence of the BAP1 mutation.
“In summary, we found that PFS-2 was significantly worse in patients with BAP1 alteration compared with patients who had unaltered BAP1. However, the interaction test did not indicate that there's a significant advantage to either IO/IO or TK/IO in treating BAP1-altered patients in the first line,” Fitzgerald said. “We did not identify a discrete genomic biomarker to guide first-line regimen selection and clinical stratification remains key for this purpose.”
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Fitzgerald K, et al. Abstract 4545. Presented at: ASCO Annual Meeting; June 2-6, 2022; Chicago.
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