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Expert Discusses Treatment Options in Advanced CRC

Angelica Welch
Published Online: Monday, Nov 13, 2017

However, it was an eye-opening study in terms of you should consider providing a BRAF inhibitor to patients as part of a clinical trial. Also, testing for BRAF mutations encouraged individuals to test their patients’ tumors for the presence of BRAF mutations. Keep in mind, this is not the BRAF mutation that is associated with hypermethylation for microsatellite instability (MSI). 

There are other trials; there have been a lot of phase I and phase II trials. There is an ongoing phase III trial regarding the BRAF mutation that is a pharmaceutical-sponsored study.

The combination of dabrafenib (Tafinlar) and trametinib (Mekinist) has been tried in various solid tumors. Is MEK also expressed in CRC where this treatment might be an option?

MEK by itself is not effective, but we are looking at MEK inhibitors in combination with a lot of PD-1/PD-L1 inhibitors in several ongoing trials. Dr Johanna Bendell is the primary investigator in one of the studies, and I am an investigator in a study as well that is looking at the role of immunotherapy and MEK inhibitors in combination.

Are we looking at any specific targeted therapies for patients with HER2 amplification?

There were some data from the Fondazione del Piemonte per l'Oncologia, looking at lapatinib (Tykerb) specifically in that setting, and we saw a response rate greater than 30%. The SWOG study is basically looking at pertuzumab (Perjeta) in combination, with the hope that they find some promising results, as well. 

What does the next 5 years in this landscape look like to you?

I would definitely say that, for the refractory setting, we are going to continue to swing away from cytotoxic chemotherapy, and, hopefully, move forward to more immune-modulated agents. [This will not be] necessarily as single agents, but in combinations, especially in the RAS-mutant and MSI patient populations.


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