Mastering Mutation-Driven mCRC: From Testing to Targeted Therapy

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Dr. Seligmann:

Hello, this is CME on ReachMD. I'm Dr. Jenny Seligmann. I'm very pleased to be joined for this episode by Dr. Fortunato Ciardiello.

We're going to be discussing a patient case example. What can you tell us about your patient?

Dr. Ciardiello:

Thank you, Jenny.

The case I will discuss with you is relatively challenging. She was around 70 years of age, and unfortunately, she had a major neurological disorder from several years that was multiple sclerosis, for which she had active treatment.

She had symptoms of right-sided located primary tumor, a classical symptomatic disease for that localization, and the tumor was localized. So as first treatment, she went to surgery. She had a right-sided hemicolectomy with nodular excision as appropriate. But unfortunately, although it was intended as a radical oncological excision, really the tumor had metastatic spread, being in the peritoneum.

This is a typical situation about BRAF-mutant disease. In fact, the tumor was BRAF V600E mutant and was with high microsatellite instability. Therefore, in the choice of first-line treatment, we thought at the time of using an anti-PD1 antibody, that is in this case pembrolizumab. So the lady started pembrolizumab, but unfortunately, after a couple months of treatment, she had a rapid clinical deterioration and disease progression and actually had to stop the treatment.

Before starting second line, she even went to having an occlusion, and she went to the emergency room for surgery. Terminal ileostomy was located, and the lady had diffuse peritoneal disease. We started combination of encorafenib plus cetuximab. And this was our choice because the patient had a BRAF-mutant tumor. Although she never did chemotherapy, we thought the most appropriate second line for this particular case was the combination. And actually, the therapy succeeded because at the first reevaluation, she had a stable disease, and after 4 months of starting treatment, she had a partial response.

Within 8 to 10 months of treatment, she had a complete radiological response, and very good clinical conditions. She had, after about 7 to 8 months of treatment, G3 diarrhea, and we started one dose reduction from cetuximab, and after another 6 or 7 months, we did a second dose reduction for both drugs. But since then, she's still on treatment, and apparently in complete response.

Dr. Seligmann:

I completely agree with your decision to go straight from immunotherapy to BRAF-targeted therapy. I think you needed a response, and I think you were most likely to get a response with EC, so I completely agree. 

So anti-EGFR-related rashes can be quite difficult to manage, but what I find in my practice, is that the people that really need to be involved in the management is the multidisciplinary team and, indeed, the patient themselves. So I encourage my patients, when I'm starting these drugs, to really take a very proactive approach to their skin management. So you make them aware of what might happen. You make them aware that there's things that they could do that may reduce the chances of developing a severe rash, so such as sun care, good emollient use, avoiding irritants. And also, really importantly, to let us know soon if they are developing a rash. And if we can implement effective treatment earlier, it can lead to not having to de-escalate doses or avoiding dose reductions.

There's several strategies, and there's a very stepwise approach to treating these rashes. They're very much protocolized, starting out with emollients, topical steroids, other topical agents, such as lymecycline. Sometimes people will give prophylactic antibiotics. 

And, indeed, sometimes you do have to interrupt treatment. And if there's a grade 3 reaction, certainly you need to interrupt until it deescalates to grade 1 or 2.

So that's all we have time for. So thank you very much, Fortunato. It’s been a pleasure.

Dr. Ciardiello:

Thank you, Jenny. It has been really a pleasure for me. 

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