Danny Nguyen, MD, discusses an analysis of efficacy and adverse events of mobocertinib in patients with EGFR-positive non–small cell lung cancer that was presented at the European Society for Medical Oncology 2021 Congress.
Danny Nguyen, MD, assistant clinical professor at the department of medical oncology & therapeutics research at City of Hope, discusses an analysis of efficacy and adverse events (AEs) of mobocertinib (Exkivity) in patients with EGFR-positive non–small cell lung cancer (NSCLC) that was presented at the European Society for Medical Oncology 2021 Congress.
The phase 1/2 study (NCT02716116) administered 160 mg daily of mobocertinib, an oral EGFR/HER2 inhibitor, to patients who were pretreated with platinum-based chemotherapy. Dose reductions due to AEs were required in 29 of 114 patients, and 21 of these 29 needed a lower dose due to gastrointestinal (GI) toxicity. According to Nguyen, investigators reported diarrhea in 91% of patients and grade 3 or 4 diarrhea in 21%. Nausea was observed in 34% and vomiting in 30%.
Nguyen says that the exposure-safety analysis showed that the overall response rate (ORR) was 21% (95% CI, 8.0-39.7) in patients who needed dose reductions due to AEs, compared with 31% (95% CI, 21.1-41.5) in those who did not require dose reductions. The duration of response (DOR) was 5.7 months (95% CI, 3.7-not reached [NR]) compared with 17.5 months (95% CI, 7.4-NR), and progression-free survival (PFS) was 5.9 months (95% CI, 3.7-11.0) compared with 7.3 months (95% CI, 5.5-10.8) in patients who did not need dose reductions. The efficacy of mobocertinib was demonstrated to be linked to the level of exposure, leading to reduced efficacy in dose reductions.
0:08 | What we found was that most of the GI toxicities were low grade in severity; diarrhea was the most common GI toxicity in 93% of patients, all-grade diarrhea was observed in 91% of patients, with grade 3 or 4 diarrhea observed in 21% of patients. Thirty-four percent of patients experienced nausea and 30% of patients experienced vomiting. The median time to onset of diarrhea was approximately 5 days, all-grade diarrhea typically resolved in about 2 days, with grade 3 diarrhea resolving in about 6 and a half days or a week. Almost three-quarters of patients were on some form of anti-diarrheal medication: more commonly, loperamide.
So what we found when analyzing all the patients who experienced diarrhea and dose modifications was that the ORR of mobocertinib was approximately 21% of patients who experienced AEs leading to dose reductions. Whereas compared that to an ORR of 31% in those patients without AEs leading to dose reductions. We also found that PFS was lower in these patients: 5.9 months versus 7.3 months. And the DOR was also lower: about 6 months compared to 17.5 months.