Characterization and management of adverse events observed with mobocertinib (TAK-788) treatment for EGFR exon 20 insertion–positive non–small cell lung cancer Review
| Authors: | Yang, J. C. H.; Zhou, C.; Jänne, P. A.; Ramalingam, S. S.; Kim, T. M.; Riely, G. J.; Spira, A. I.; Piotrowska, Z.; Mekhail, T.; Garcia Campelo, M. R.; Felip, E.; Bazhenova, L.; Jin, S.; Kaur, M.; Diderichsen, P. M.; Gupta, N.; Bunn, V.; Lin, J.; N. Churchill, E.; Mehta, M.; Nguyen, D. |
| Review Title: | Characterization and management of adverse events observed with mobocertinib (TAK-788) treatment for EGFR exon 20 insertion–positive non–small cell lung cancer |
| Abstract: | Background: Mobocertinib has demonstrated durable clinical benefit in platinum-pretreated patients (PPP) with epidermal growth factor receptor exon 20 insertion–positive non–small cell lung cancer (NSCLC). Research design and methods: Pooled safety analysis of two studies included patients with NSCLC (N = 257) treated with the recommended phase 2 dose (RP2D) of mobocertinib (160 mg once daily). We report overall safety (treatment-emergent adverse events [TEAEs]) in the RP2D population; characterization of GI and skin-related events in 114 PPP from a phase 1/2 study (NCT02716116); and clinical activity in PPP with and without dose reductions due to TEAEs. Results: In the RP2D population (N = 257), the most common TEAEs were diarrhea (93%), nausea (47%), rash (38%), and vomiting (37%). In PPP (N = 114), median times to diarrhea onset and resolution were 5 and 2 days, respectively. Median times to onset and resolution of skin-related events were 9 and 78 days, respectively. Among PPP with (n = 29) or without (n = 85) dose reductions due to TEAEs, overall response rates were 21% and 31% and median durations of response were 5.7 and 17.5 months, respectively. Conclusions: GI and skin-related events are common with mobocertinib; minimizing dose reductions with proactive management may improve clinical outcomes. Trial Registration: NCT02716116; NCT03807778. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. |
| Keywords: | antibiotic agent; gene mutation; exon; genetics; mutation; clinical trial; constipation; disease course; fatigue; diarrhea; dose response; drug dose reduction; drug safety; hypertension; hypophosphatemia; recommended drug dose; side effect; skin manifestation; drug eruption; phase 2 clinical trial; anemia; protein kinase inhibitor; gastrointestinal symptom; mucosa inflammation; nausea; stomatitis; vomiting; carcinoma, non-small-cell lung; lung neoplasms; dehydration; fluid therapy; incidence; qt prolongation; epidermal growth factor receptor; body weight; patient education; creatinine; creatinine blood level; protein tyrosine kinase; alanine aminotransferase blood level; aspartate aminotransferase blood level; backache; drug fever; dyspnea; hypomagnesemia; lymphocytopenia; pneumonia; pruritus; protein kinase inhibitors; hypoxia; lung tumor; alanine aminotransferase; aspartate aminotransferase; acute kidney failure; hypokalemia; hyponatremia; maculopapular rash; patient care; population research; antiinfective agent; statistical analysis; acne; patient safety; carcinoma; xerostomia; platinum; sex difference; loperamide; diet therapy; probiotic agent; dermatitis; headache; age distribution; phase 1 clinical trial; egfr gene; gene insertion; gastroesophageal reflux; abnormally high substrate concentration in blood; amylase blood level; dyspepsia; triacylglycerol lipase blood level; dry skin; minocycline; alopecia; fluid intake; treatment withdrawal; physical performance; drug induced disease; amylase; egfr protein, human; drug exposure; race; paronychia; triacylglycerol lipase; respiratory failure; clobetasol; triamcinolone; non small cell lung cancer; mouth ulcer; decreased appetite; feces culture; hypertransaminasemia; petrolatum; hyperamylasemia; rhinorrhea; body weight loss; erbb receptors; humans; human; article; drug-related side effects and adverse reactions; treatment response time; protein tyrosine kinases; mobocertinib; non–small cell lung; betamethasone valerate; hydrocortisone valerate; epidermal growth factor receptor exon 20 insertion positive non small cell lung cancer |
| Journal Title: | Expert Review of Anticancer Therapy |
| Volume: | 23 |
| Issue: | 1 |
| ISSN: | 1473-7140 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2023-01-01 |
| Start Page: | 95 |
| End Page: | 106 |
| Language: | English |
| DOI: | 10.1080/14737140.2023.2157815 |
| PUBMED: | 36537204 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2023 -- Source: Scopus |
