Robust anticancer activity of trastuzumab deruxtecan in HER2-mutated NSCLC

Primary data from the DESTINY-Lung01 trial demonstrated trastuzumab deruxtecan (T-DXd) to be safe and effective in heavily pretreated patients with HER2-mutated non-small cell lung cancer (NSCLC).

HER2 mutations occur in ∼3% of patients with NSCLC, indicating poor prognosis and an increased incidence of brain metastases [1]. T-DXd is a novel antibody-drug conjugate consisting of a humanised, anti-HER2 monoclonal antibody, a topoisomerase I inhibitor payload, and an exatecan derivative [2]. The phase 2 DESTINY-Lung01 trial (NCT03505710) assessed the efficacy and safety of T-DXd in heavily pretreated (up to 8 lines) patients with HER2-mutated NSCLC.

A total of 91 patients (median age 60 years; 93.4% had a HER2 mutation; 36.3% had asymptomatic central nervous system metastasis) were treated with T-DXd (6.4 mg/kg every 3 weeks). Primary endpoint was objective response rate (ORR), secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Dr Bob Li (Memorial Sloan Kettering Cancer Center, NY, USA) presented the primary data [3].

Centrally confirmed ORR was 54.9% (49 partial responders, 1 complete responder); disease control rate was 84%. Responses were observed across all HER2 mutation subtypes, as well as in patients with no detectable HER2 expression or HER2 gene amplification. Efficacy was consistent across subgroups, including patients previously treated with a HER2 tyrosine kinase inhibitor or with brain metastasis. Median PFS was 8.2 months; median OS was 17.8 months.

Treatment-related adverse events (any grade) occurred in 96.7% of patients, treatment-related adverse events grade ≥3 were observed in 46.2% of patients. Adjudicated drug-related interstitial lung disease (ILD) occurred in 24 patients.

“T-DXd demonstrated robust and durable activity in patients with previously treated HER2-mutated NSCLC,” concluded Dr Li. “T-DXd has a manageable safety profile; however, ILD remains an important risk. Effective early detection and management are critical in preventing high-grade ILD.”

1. Offin M, et al. Cancer. 2019;125:4380-4387.
2. Ogitani Y, et al. Clin. Cancer Res. 2016;22:5097–5108.
3. Li B, et al. Primary data from DESTINY Lung01:a phase 2 trial of trastuzumab deruxtecan (T DXd) in patients with HER2 mutated ( HER2 m) metastatic non small cell lung cancer (NSCLC). Abstract LBA45, ESMO Congress 2021, 16–21 September.

 

Copyright ©2021 Medicom Medical Publishers



Posted on 19 November 202129 February 2024