Dr. Joseph on Molecular Signatures in mRCC

Richard W. Joseph, MD
Published: Tuesday, Sep 03, 2019



Richard W. Joseph, MD, internist and oncologist, Mayo Clinic, discusses molecular signatures in metastatic renal cell carcinoma (mRCC).

Current molecular signatures can be used to distinguish a VEGF-based tumor from an immune tumor, says Joseph. Now that the majority of frontline treatment regimens in mRCC are combinations of immunotherapy and VEGF therapies, great signatures to distinguish between regimens are lacking. Prior to immunotherapy and VEGF combinations, PD-L1 was relatively helpful, adds Joseph; now, it’s less helpful, but not obsolete. For example, a PD-L1–positive tumor—especially in patients with sarcomatoid histology—would do better with a double immunotherapy combination. The responses that have been reported with the combination of ipilimumab (Yervoy) and nivolumab (Opdivo) in patients with PD-L1–positive sarcomatoid tumors are very high. However, as it stands, a treatment decision should never be based solely on PD-L1, he says.

Joseph is hopeful that molecular markers will emerge, especially for PD-L1–negative patients, in whom treatment approaches between a double immunotherapy combination versus an immunotherapy/VEGF combination are not always as clear.
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Richard W. Joseph, MD, internist and oncologist, Mayo Clinic, discusses molecular signatures in metastatic renal cell carcinoma (mRCC).

Current molecular signatures can be used to distinguish a VEGF-based tumor from an immune tumor, says Joseph. Now that the majority of frontline treatment regimens in mRCC are combinations of immunotherapy and VEGF therapies, great signatures to distinguish between regimens are lacking. Prior to immunotherapy and VEGF combinations, PD-L1 was relatively helpful, adds Joseph; now, it’s less helpful, but not obsolete. For example, a PD-L1–positive tumor—especially in patients with sarcomatoid histology—would do better with a double immunotherapy combination. The responses that have been reported with the combination of ipilimumab (Yervoy) and nivolumab (Opdivo) in patients with PD-L1–positive sarcomatoid tumors are very high. However, as it stands, a treatment decision should never be based solely on PD-L1, he says.

Joseph is hopeful that molecular markers will emerge, especially for PD-L1–negative patients, in whom treatment approaches between a double immunotherapy combination versus an immunotherapy/VEGF combination are not always as clear.



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