From the Journals

T-DM1 produces 44% response rate in HER2-mutant lung cancers

 

Key clinical point: Ado-trastuzumab emtansine (T-DM1) demonstrated activity in advanced, HER2-mutant lung cancer.

Major finding: Confirmed partial responses were seen in 44% of patients. Median progression-free survival was 5 months.

Study details: Analysis of a cohort of 18 patients with HER2-mutant metastatic lung adenocarcinomas enrolled in a phase 2, investigator-initiated basket trial.

Disclosures: The Conquer Cancer Foundation, Genentech, and the National Institutes of Health supported the study. The researchers reported disclosures related to Roche, Biosceptre International, Thermo Fisher Scientific, Mersana, Guardant Health, Genentech, Illumina, BioMed Valley Discoveries, AstraZeneca, GRAIL, and NantOmics, among others.

Source: Li BT et al. J Clin Oncol. 2018 July 10. doi: 10.1200/JCO.2018.77.9777.


 

FROM THE JOURNAL OF CLINICAL ONCOLOGY

Ado-trastuzumab emtansine (T-DM1) has met a predefined efficacy endpoint in what investigators say is the first positive clinical trial in patients with advanced HER2-mutant lung cancers.

The HER2-targeted therapy produced a 44% overall response rate among 18 patients enrolled in the phase 2, investigator-initiated basket trial reported in the Journal of Clinical Oncology.

The median progression-free survival (PFS) was 5 months in this heavily pretreated group of patients, according to first author Bob T. Li, MD, of Memorial Sloan Kettering Cancer Center, New York, and his coauthors.

“This is important therapeutic progress in the context of more than a decade of negative clinical trials targeting HER2 in lung cancer,” the researchers wrote.

The patients (median age, 64 years; 72% female) had metastatic lung adenocarcinomas treated in 2016 at Memorial Sloan Kettering Cancer Center. All patients had HER2-activating mutations identified by next-generation sequencing. They had received a median of two lines of prior therapy. Three of the 18 patients were treatment naive. Prior HER2-targeted therapy, including trastuzumab, was allowed.

All patients received intravenous infusions of T-DM1 at 3.6 mg/kg every 21 days until progression of disease or unacceptable toxicity.

Confirmed partial responses were seen in 8 patients (44%), while an additional 7 (39%) had stable disease, Dr. Li and his coauthors reported. Median PFS was 5 months overall and 6 months for responders, with the longest observed PFS being more than 11 months.

The treatment was well tolerated, with treatment-related adverse events mainly consisting of grade 1-2 infusion reactions, elevation of hepatic transaminases, and thrombocytopenia.

The rate of infusion reactions was higher than what was expected based on the experience with T-DM1 in breast cancer, though these reactions were generally mild and did not require discontinuation of the drug, which is approved for the treatment of HER2-amplified or –overexpressing metastatic breast cancer.

These findings have important implication for drug development in HER-2 mutant lung cancers, particularly as next-generation sequencing becomes more commonly used for initial tumor evaluation, Dr. Li and his coauthors noted.

“Just as the discovery of EGFR mutations eventually led to a plethora of approved oncogene-targeted therapies transforming the care of patients around the world, HER2-activating mutations similarly show promise as a therapeutic target,” they wrote.

Disappointing results were seen in previous studies looking at trastuzumab in lung cancer patients, and in those trials, patients were selected on the basis of HER2 protein expression by immunohistochemistry (IHC). “More recent studies have again confirmed that HER2 IHC is not the ideal biomarker in lung cancers,” the researchers wrote.

The 18-patient cohort in this study was part of a larger, investigator-initiated basket trial. Cohorts not reported at this time involved patients with other HER2-amplified solid tumors, including bladder.

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

Dr. Li reported disclosures related to Roche, Biosceptre International, Thermo Fisher Scientific, Mersana, Guardant Health, Genentech, Illumina, BioMed Valley Discoveries, AstraZeneca, and GRAIL. Several co-authors reported disclosures, including employment, with NantOmics, a developer of molecular profiling tools.

SOURCE: Li BT et al. J Clin Oncol. 2018 July 10. doi: 10.1200/JCO.2018.77.9777.

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