Dr. Lieu Discusses the Rationale for Combined MEK/VEGF/PD-1 Inhibition in CRC

Christopher Lieu, MD
Published: Wednesday, Aug 07, 2019



Christopher Lieu, MD, director, GI Medical Oncology Program and deputy associated director for clinical research, at the University of Colorado Cancer Center, discusses the rationale for combined MEK, VEGF, and PD-1 inhibition in microsatellite stable (MSS) colorectal cancer (CRC).

One of the main challenges in pursuing immunotherapy in MSS CRC is that immune cells are not close to the tumor or inside the tumor, says Lieu. Therefore, a lot of work has gone into figuring out how to bring immune cells to the tumor.

An emerging strategy is to use 2 targeted therapies—binimetinib (Mektovi) and bevacizumab (Avastin)—to bring more immune cells to the tumor. The addition of a PD-1 inhibitor may further increase this activity, leading to synergistic antitumor activity, explains Lieu. Right now, the MEK inhibitor binimetinib, is being tested in combination with the VEGF inhibitor bevacizumab, and the PD-1 inhibitor pembrolizumab. The safety lead-in of the trial has already been completed and has shown some promising results. Now, the regimen is being moved to a phase II trial, concludes Lieu.
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Christopher Lieu, MD, director, GI Medical Oncology Program and deputy associated director for clinical research, at the University of Colorado Cancer Center, discusses the rationale for combined MEK, VEGF, and PD-1 inhibition in microsatellite stable (MSS) colorectal cancer (CRC).

One of the main challenges in pursuing immunotherapy in MSS CRC is that immune cells are not close to the tumor or inside the tumor, says Lieu. Therefore, a lot of work has gone into figuring out how to bring immune cells to the tumor.

An emerging strategy is to use 2 targeted therapies—binimetinib (Mektovi) and bevacizumab (Avastin)—to bring more immune cells to the tumor. The addition of a PD-1 inhibitor may further increase this activity, leading to synergistic antitumor activity, explains Lieu. Right now, the MEK inhibitor binimetinib, is being tested in combination with the VEGF inhibitor bevacizumab, and the PD-1 inhibitor pembrolizumab. The safety lead-in of the trial has already been completed and has shown some promising results. Now, the regimen is being moved to a phase II trial, concludes Lieu.

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