, an investigator reported.
The overall response rate (ORR) exceeded 60% among these heavily pretreated patients, with an estimated median progression-free survival (PFS) of 14 months, according to Egbert F. Smit, MD, PhD, of the Netherlands Cancer Institute.
Interstitial lung disease is an identified risk associated with T-DXd treatment, though the events in the DESTINY-Lung01 trial have been low-grade and have not resulted in any deaths, Dr. Smit said when presenting results from the trial as part of the American Society of Clinical Oncology virtual scientific program.
“These data demonstrate the potential of T-DXd as a new treatment option for patients with HER2-mutated non–small-cell lung cancer,” Dr. Smit said.
‘A good targeted therapy’
The findings are a “nice early confirmation” of the initial results seen with T-DXd in an earlier, smaller, phase 1 population, said invited discussant Grace K. Dy, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.
“Trastuzumab-DXd showed clinical outcomes that meet the standards of what we expect a good targeted therapy should have in terms of overall response rate and progression free survival,” Dr. Dy said.
She noted that the ORR in DESTINY-Lung01 exceeds a 23% ORR seen among NSCLC patients treated with dual HER2-targeted therapy – trastuzumab plus pertuzumab – in a basket trial (J Clin Oncol. 2018 Feb 20;36[6]:536-42). Moreover, the response and PFS data “far surpass” results seen to date with oral tyrosine kinase inhibitors, including pyrotinib, poziotinib, neratinib, and afatinib.
The T-DXd results also look favorable in comparison to another antibody-drug conjugate, ado trastuzumab emtansine, Dr. Dy added, referencing another basket trial in which investigators reported an ORR of 44% and a median PFS of 5 months among 18 patients with advanced HER2-mutant lung adenocarcinomas (J Clin Oncol. 2018 Aug 20;36[24]:2532-7).
“Although T-DM1 [ado trastuzumab emtansine] demonstrated some degree of activity, its lower dosing, which was limited by the payload, lower drug-antibody ratio, and shorter half-life likely explain why results were better with T-DXd,” Dr. Dy said.
T-DXd was, in fact, designed to deliver an optimal antitumor effect, according to Dr. Smit.
The treatment incorporates a humanized anti-HER2 IgG1 monoclonal antibody that has the same amino acid sequence as trastuzumab. The antibody is attached via a cleavable, tumor-selective linker to a payload of deruxtecan, a topoisomerase I inhibitor.
The resulting antibody-drug conjugate has a high drug-to-antibody ratio, with 8 DXd molecules per monoclonal antibody, according to Dr. Smit.