EGFR Exon 20–Directed Therapy With Mobocertinib

Mark A. Socinski, MD: At the recent ASCO [American Society of Clinical Oncology Annual Meeting] presentation with 1 of the new agents, specifically the exon 20 insertion mutations, we heard from Suresh Ramalingam, who was focusing on mobocertinib, or what I still call TAK-788. This was an update including patients who were in what was called the EXCLAIM cohort. These were patients who were previously treated with platinum-based treatment. This ended up including some of the patients from the dose-escalation part of the trial. At the end of the day, there are about 114 patients who were reported on in this setting, using a daily dose of 160 mg of mobocertinib. All these patients were previously treated, and 90% or more of them had had a platinum-containing regimen in the past. What they showed was a confirmed overall response rate of 28% in this population. What was remarkable about the responses is the median duration of response, which was about 17½ months; median progression-free survival, which was just over 7 months; and impressively, the median overall survival, which was about 24 months.

The overall response rate of 28% is not that impressive. We’re used to seeing these driver populations have response rates well north of 50%. It bears looking at the waterfall plot. When you look at the waterfall plot, you realize that even though the objective response rate was only 28%, the vast majority of these patients were having what I would consider clinically significant and clinically relevant shrinkage of their target lesions, which we think is a benefit in these patients. This is a situation where the overall or objective response rate underestimates what the clinical utility of the drug may be. I pointed this out before, but it was quite remarkable that the duration of response was nearly 18 months in this population.

The toxicity profile was what you would expect from an EGFR TKI [tyrosine kinase inhibitor]. Grade 3 diarrhea was the primary problem, and it occurred in about 20% of patients. Skin rash was almost exclusively grade 1 or 2, so it wasn’t a major issue. Another important aspect of the presentation was the patient-reported outcomes, which suggested that patients were benefiting by having reduction in the typical disease-related symptoms. Their overall global quality-of-life analysis showed that there was no detriment. I have to admit there were some GI [gastrointestinal] issues probably related to the diarrhea that were obviously of concern to patients in these patient-reported outcomes, but overall there were no surprises. Given the level of activity relative to the adverse events that were reported, this is an important potential addition to this population of patients.

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