Dr Neal outlines second-line targeted treatment selection for the patient case, while Lauren Welch, MSN, NP-C, AOCNP, shares her experience with managing the adverse effects of mobocertinib in patients with EGFR exon 20-mutated mNSCLC and comments on potential strategies for treatment modification.
Joel Neal, MD, PhD: This patient was started on mobocertinib 160 milligrams daily. As Lauren and Zosia talked about, talked about adverse events prophylactically given medicines such as loperamide, for diarrhea, scheduled for frequent follow-ups came back with grade two diarrhea seven days later. We don't usually grade diarrhea outside of a clinical trial, but that grading is, I believe, four to six stools per day over what the baseline would've been for a patient, assuming one or two usually at baseline. We talked about the common adverse events for mobocertinib and much of the management of this. It really is important to have that prophylactic management of diarrhea as well as for those of us fortunate enough to have what we call at least supportive dermatologic oncologists who know about all of the different creams and everything else to try and manage the skin side effects. Sometimes it's antibiotics, sometimes it's steroids and it's always lots of moisturizer is what I've concluded; face, chest, and back. And just like the old days of first-generation EGFR TKIs, we tell patients rash is good, but treating rash is also good and getting rid of it is OK. What's the frequency of dose reductions that you have to do, Zosia? Are you able to maintain most patients on 160 or do they end up coming down?
Zosia Piotrowska, MD: Variable. I would say as you alluded to, we try to continue on 160, but it's been variable in my experience as to whether patients can continue on. And I think that you can only try to a certain extent if patients are having ongoing issues, particularly with GI toxicities, with diarrhea, with nausea, they're losing weight. I think that that's not a sustainable strategy for someone to stay on treatment for a longer period of time. And patients are often hesitant for dose reductions. And I think in those situations I try to explain to them, the idea is really to find a dose that's going to allow them to stay on that therapy and to be able to stay on it for as long as possible. And sometimes dose reduction is the way to do that. I would say it's not the majority of patients, but we certainly do have patients where it just feels like 160 is too much for them. And in those patients, I do feel OK about reducing to 120 and I find that that can be really helpful in terms of many of these side effects.
Joel Neal, MD, PhD: Lauren talked about grading, and I know one thing that I've done in practice outside of clinical trials where we have to grade everything and manage it according to the protocol. But otherwise, what I'll often come down to is it tolerable or intolerable for the patient? And asking them directly, sometimes we don't get a straight answer, but offering a dose hold or a dose reduction if they agree to that you know it's intolerable. Do you prefer holding it until everything gets better or do you just go straight to the dose reduction? Or is there some mix of techniques you use?
Lauren Welch, MSN, NP-C, AOCNP: Yes. It depends on the severity; how sick they appear. And also, we see such a variety of patients and patients that have various support systems in place, caregivers. Some are not the best historians. Some they have a harder time with an oral therapy. When we were doing the mobocertinib trials one of the patients I had on this trial was a mother of seven who lived five hours away and was a terrible historian probably because she had seven kids that she was trying to keep up with. And it was so difficult really drilling in on, “How are you using your loperamide?” or, “Are we really optimally doing the antidiarrheals like we need to?” And if you think about the four pills a day for the mobocertinib and then we're tacking on how many more loperamide capsules and that's not even considering the other medications people are on. They easily get pill fatigue. And so, I have a low threshold [for holding medication]. Once your diarrhea has subsided, you're feeling more like yourself, we've got you hydrated, then we'll rechallenge. And I really just take that patient by patient. If I know that they'll call me and I feel like we've got that- I've got that security, then we may try the same 160 and see if it goes better with more aggressive prophylactic antidiarrheals.
Joel Neal, MD, PhD: Yeah, I think it's a discussion with the patient, but all those techniques and strategies are valuable.