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Targeting HER2 Mutations in NSCLC With Triplet Therapy

By: Lauren Harrison, MS
Posted: Friday, April 8, 2022

For patients with HER2-mutated advanced non–small cell lung cancer (NSCLC), combination therapy using trastuzumab, pertuzumab, and docetaxel is both feasible and effective. Julian Mazieres, MD, PhD, of Toulouse University Hospital, France, and colleagues published the results of this phase II study in the Journal of Clinical Oncology.

“As there is no standard of care regarding targeted therapy in patients presenting HER2-mutated non–small-cell lung cancer, our combination could be considered as a potential option,” stated the authors.

This multicenter trial enrolled 45 patients with HER2-mutated NSCLC who had disease progression after at least one platinum-based therapy. Patients received a loading dose of 840 mg of pertuzumab, followed by 420-mg doses afterward. Trastuzumab was administered at an 8-mg/kg loading dose and a 6-mg/kg therapeutic dose, and 75 mg/m2 of docetaxel was given every 3 weeks.

The median duration of treatment was 4.9 months, and the median follow-up was 12 months. The objective response rate was 29%, and 58% of patients had stable disease. The median progression-free survival was 6.8 months, and the median duration of response was 11 months. The median overall survival was 17.6 months. At the time of data collection, 15 patients were still receiving treatment.

Grade 3 or 4 adverse events were noted in 64% of patients; however, no patient discontinued therapy due to toxicity. The most common grade 3 or higher treatment-related adverse events included neutropenia (33%), diarrhea (13%), and anemia (9%). No cases of interstitial lung disease were reported. Among the 19 patients who had previously received immunotherapy, there was no evidence of greater toxicity compared with those without prior immunotherapy. 

Disclosure: For a full list of authors’ disclosures, visit ascopubs.org.


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