Dr. Powles on PD-L1 as a Biomarker in RCC

Thomas Powles, MD, MBBS, MRCP
Published: Friday, May 24, 2019



Thomas Powles, MD, MBBS, MRCP, professor, Genitourinary Oncology, lead for Solid Tumour Research, and director, Barts Cancer Institute, discusses the use of PD-L1 as a biomarker in renal cell carcinoma (RCC).

The results of the phase III KEYNOTE-426 study showed that the combination of pembrolizumab (Keytruda) and axitinib (Inlyta) was effective in patients with advanced RCC, irrespective of International Metastatic Renal Cell Carcinoma Database Consortium risk group and PD-L1 status. However, due to contradictory data, there is a lot of uncertainty with the biomarker, says Powles. If patients receive the combination of a VEGF-targeted therapy and immunotherapy, they’re getting the antiangiogenic effect, which may dilute the effect of the PD-L1 biomarker. Therefore, at this time, PD-L1 is not an appropriate biomarker by which to select patients for the combination of pembrolizumab and axitinib, he explains.

In terms of emerging biomarkers, the strongest data have come from the phase II IMmotion150 and phase III IMmotion151 trials with the combination of bevacizumab (Avastin) and atezolizumab (Tecentriq). Those trials used RNA sequencing and FoundationOne CDx to look for gene signatures and mutations associated with response and resistance. Investigators identified distinct angiogenic signatures and T-effector gene signatures associated with response to VEGF-targeted therapies and immunotherapies, respectively. That work needs to be validated, but it is a huge contribution to the field that may lead to an increase in personalized medicine in the future.
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Thomas Powles, MD, MBBS, MRCP, professor, Genitourinary Oncology, lead for Solid Tumour Research, and director, Barts Cancer Institute, discusses the use of PD-L1 as a biomarker in renal cell carcinoma (RCC).

The results of the phase III KEYNOTE-426 study showed that the combination of pembrolizumab (Keytruda) and axitinib (Inlyta) was effective in patients with advanced RCC, irrespective of International Metastatic Renal Cell Carcinoma Database Consortium risk group and PD-L1 status. However, due to contradictory data, there is a lot of uncertainty with the biomarker, says Powles. If patients receive the combination of a VEGF-targeted therapy and immunotherapy, they’re getting the antiangiogenic effect, which may dilute the effect of the PD-L1 biomarker. Therefore, at this time, PD-L1 is not an appropriate biomarker by which to select patients for the combination of pembrolizumab and axitinib, he explains.

In terms of emerging biomarkers, the strongest data have come from the phase II IMmotion150 and phase III IMmotion151 trials with the combination of bevacizumab (Avastin) and atezolizumab (Tecentriq). Those trials used RNA sequencing and FoundationOne CDx to look for gene signatures and mutations associated with response and resistance. Investigators identified distinct angiogenic signatures and T-effector gene signatures associated with response to VEGF-targeted therapies and immunotherapies, respectively. That work needs to be validated, but it is a huge contribution to the field that may lead to an increase in personalized medicine in the future.

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