Ado-Trastuzumab Emtansine in HER2-Mutant Lung Cancer


Key Points

  • Response was observed in 44% of patients.
  • Responses were seen in patients with HER2 exon 20 insertions and point mutations in the kinase, transmembrane, and extracellular domains.

As reported by Li and colleagues in the Journal of Clinical Oncology, the HER2-targeted antibody-drug conjugate ado-trastuzumab emtansine (Kadcyla) showed activity in advanced HER2-mutant lung adenocarcinoma.

Study Details

The current report involves a cohort of patients with HER2-mutant lung cancer in a phase II basket trial performed at Memorial Sloan Kettering Cancer Center. Overall, 18 patients received ado-trastuzumab emtansine intravenously at 3.6 mg/kg every 3 weeks until progression. Patients had received a median of two prior systemic therapies (range = 0–4), and 50% had received prior HER2-targeted therapy.


Objective response was observed in eight patients (44%; all partial responses) and stable disease was observed in seven (39%). Responses were observed in patients with HER2 exon 20 insertions and point mutations in the kinase, transmembrane, and extracellular domains. Concurrent HER2 amplification was observed in two patients, with one having partial response and one having stable disease. HER2 immunohistochemistry ranged from 0 to 2+ and was not associated with response; responders had low HER2 protein expression on mass spectrometry. Median progression-free survival was 5 months among all patients and 6 months among responders. The longest progression-free survival (11+ months) was observed in a patient with stable disease as best response with a 27% reduction in tumor size.

Adverse Events

Toxicities included grade 1 or 2 infusion reactions (28%), thrombocytopenia (33%), and elevated hepatic transaminases (45%). All infusion reactions resolved with slowing of infusion and antihistamine treatment and did not preclude retreatment. A grade 3 adverse event (anemia) occurred in one patient. No grade 4 adverse events or deaths were observed. There were no dose reductions or discontinuations due to treatment-related adverse events.

The investigators concluded, “Ado-trastuzumab emtansine is an active agent in patients with HER2-mutant lung cancers. This is the first positive trial in this molecular subset of lung cancers. Further use and study of this agent are warranted.”

The study was supported by the Conquer Cancer Foundation, a grant from the National Institutes of Health, and Genentech.

Bob T. Li, MD, of the Thoracic Oncology and Early Drug Development Service, Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.