Cabozantinib Effective Regardless of PD-L1 Expression in RCC
PD-L1 tumor expression was found not to be a predictive biomarker for cabozantinib efficacy in mRCC.
|The following article features coverage from the European Society for Medical Oncology (ESMO) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.|
PD-L1 tumor expression status did not predict outcomes with cabozantinib among patients with advanced renal cell carcinoma (RCC), according to an analysis of the CABOSUN and METEOR trials, presented at the ESMO 2018 Congress in Munich, Germany.1
PD-L1 tumor expression is associated with better outcomes among patients with metastatic RCC treated with nivolumab and ipilimumab and may, therefore, be a biomarker.
Cabozantinib is already approved for the treatment of metastatic RCC. The aim of this study was to determine if PD-L1 tumor expression could also be a predictive biomarker for cabozantinib efficacy.
In this study, tumor tissue from 416 patients enrolled in the CABOSUN and METEOR trials was analyzed by immunohistochemistry for PD-L1 and CD45/CD163 expression. PD-L1 positivity was defined as at least 1% or higher of PD-L1-positive tumor cells or immune cells.
In the METEOR and CABOSUN trials, 29% and 23% of tumors were positive for PD-L1 expression, respectively. PD-L1 positivity was significantly associated with shorter progression-free survival (PFS) and overall survival (OS), regardless of the type of treatment.
In METEOR, the median PFS was 7.2 and 5.3 months for patients who had PD-L1 negative or positive tumors, respectively (P= .027). Median OS was 21.3 and 15.1 months in the PD-L1–negative or –positive cohorts, respectively (P= .003). In CABOSUN, the median PFS was 8.3 and 5.5 months (P= .05) and median OS was 28.1 and 20.8 months (P= .05) in the PD-L1–negative or –positive groups, respectively.
PD-L1 tumor expression, however, was not a predictive biomarker for cabozantinib efficacy. In both trials, cabozantinib improved PFS, OS, and objective response rate compared with everolimus or sunitinib, regardless of PD-L1 tumor positivity. There was no association between PD-L1 positivity and outcomes with cabozantinib when evaluated by immune cell expression of PD-L1, combined PD-L1 score, or using different PD-L1 positivity cutoffs.
The authors concluded that these results indicate that cabozantinib can continue to be used in a PD-L1–unselected population as a monotherapy or, potentially, in combination with immune checkpoint inhibitors.
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- Choueiri TK, Suarez C. PD-L1 status and clinical outcomes to cabozantinib, sunitinib, and everolimus in patients with metastatic clear-cell RCC treated on CABOSUN and METEOR clinical trials. Presented at: the ESMO 2018 Congress; Munich, Germany: October 19-23, 2018. Abstract LBA34.