Dr Joel Neal reviews data from the pivotal clinical trial leading to the FDA approval of mobocertinib for EGFR exon 20-mutated advanced or metastatic lung cancers.
Joel Neal, MD, PhD: So, moving on to the two FDA-approved agents. Two pivotal studies, one with mobocertinib, the continuation of a phase 1/2 that we participated in, and you did too Zofia. And this is the data from the prior-platinum pretreated cohort. Many patients, all of which matched the usual demographics for having EGFR mutant lung cancer. So, I'm going to stress those patients that we think might have common EGFR mutations, those are also the ones whose tumors emerge these EGFR and Exon20 insertions. The high-level data for this by central review of criteria was in the PPP cohort, the response rates confirmed objective response was 28%, slightly higher in investigator-initiated, 35% overall. Duration of a response was in the 17.5-month range, so much higher than we would have expected, that was out of the 28% of patients who responded, they could actually respond durably for seventeen-and-a-half months. And then progression-free survival of 7.3 months. So, these are the data that led to the FDA approval. There’re early hints of overall survival, looking in the 24-month or two-year range overall. Interestingly, there were subset analyses by the EGFR Exon20 mutation type, these are a wide spectrum of mutations, I think it's worth pointing out that that 763FQEA mutation, I think of it as the one really closest to Exon19, does respond to first, second, and third generation EGFR TKIs pretty easily. So, that's a special mutation, but otherwise, most of these in the 764-770s range don't respond as well but they all seem to have similar responses to mobocertinib. Adverse events are worth thinking about, the most common were diarrhea, rash, paronychia, really EGFR-directed side effects here. Rarely, QT prolongation or effects on cardiac function ejection fraction. Lauren, what's your experience with mobocertinib and managing the adverse effects for patients that are on it? The usual starting dose is 160 milligrams daily, which ends up being four pills because it comes in 40-milligram pills.
Lauren Welch, MSN, NP-C, AOCNP: So, it's a lot. Mainly because I think managing a patient on mobocertinib requires a lot of up-front education. You can do it successfully, but you have to spend the time at the beginning, I think, leaning into the diarrhea piece. If you look here, and you have it displayed, 91% all-grade, 93% all-grade, and exclaimed. So, pretty much if you take this drug you're getting diarrhea, it's just how bad is it going to be, and what can we do to minimize it, right? So, this is the kind of drug where I'm telling the patient to pick up their loperamide the same day or already have it at home when they're getting their drug, we talk about how to use antidiarrheals, prophylactically even. The diarrhea tends to hit quickly, within the first several days of being on the drug, does resolve within two or three days of holding. So, I think talking to the patient about it in advance, preparing them for it, getting a good understanding on what their baseline is, patients are sometimes hesitant to talk about their bowel habits, so we kind of rip the band-aid off, and I just say, "I'm going to ask you every time you come in about your poop," and try to just put it all out there. The diarrhea is the big one because it impacts everybody, but I think for most patients if you encourage at the beginning transparency, if you tell me how you're doing, there's a better chance I can keep you on this therapy and promoting them reaching out with any issues, people are more successful that way. And then not to be diminished, is the nausea, some of the other EGFR effects like rash, but if you're nauseous and you're having grade three diarrhea, you're miserable. So, I think warning people in advance, making sure they know how to get in touch with you, and then setting up an early follow-up, maybe with some prophylactic IV fluids scheduled, just to give them a lot of TLC early on. A lot of this will even out with time as the patient gets used to it.
Joel Neal, MD, PhD: I think the nausea may be clinical or even sub-clinical, sometimes leading to decreased appetite and weight loss, I think the diarrhea and the weight loss, and everything go together. But I am hesitant to reduce the dose, I'll try to start at 160, there were some data that said that people who maintain 160 have a longer duration of response than ones who get dose reduced because I think we're very close to the threshold of inhibition of this protein.