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ESMO 2021: Primary Results From DESTINY-Lung01 on T-DXd in HER2-Mutated Lung Cancer

By: Vanessa A. Carter, BS
Posted: Friday, September 24, 2021

Primary data from the phase II DESTINY-Lung01 trial demonstrate “durable” activity with the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in previously treated patients with HER2-mutated non–small cell lung cancer (NSCLC). Bob T. Li, MD, of Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, and colleagues presented these international clinical trial results during the European Society for Medical Oncology (ESMO) Congress 2021 (Abstract LBA45); they were also simultaneously published in The New England Journal of Medicine.

“In this multicenter international trial, treatment with trastuzumab deruxtecan demonstrated a high response rate and durable clinical benefit in patients with advanced HER2-mutant NSCLC,” stated senior study author Pasi Jänne, MD, PhD, of the Dana-Farber Cancer Institute, Boston, in an institutional press release. “It shows clear potential as a targeted therapy for this hard-to-treat cancer.”

This trial enrolled 91 patients with HER2-mutated, metastatic NSCLC who were refractory to standard treatment. Participants were administered 6.4 mg/kg of T-DXd.

The median follow-up was 13.1 months, and the median number of prior therapies was two; 94.5% of patients received platinum-based therapy, and 65.9% received PD-1/PD-L1 therapy. The majority (93.4%) of individuals had an HER2 kinase domain mutation, and 36.3% had asymptomatic metastasis of the central nervous system that did not require ongoing treatment.

The objective response rate was 54.9%, with one patient (1.1%) achieving a complete response and the others (52.8%) achieving a partial response. Stable disease was achieved in 34 individuals, and 3 patients experienced disease progression, yielding a disease control rate of 92.3%. With a 9.3-month median duration of response, median progression-free survival and overall survival were 8.2 and 17.8 months, respectively.

Approximately 96.7% of patients experienced treatment-related adverse events, with almost half (46.2%) being grade 3 or above. Additionally, adverse events associated with dose interruption, reduction, and discontinuation were reported in 31, 29, and 23 patients, respectively.

Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.



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