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15-09-2022 | ESMO 2022 | Conference coverage | News

​​​​​​​‘Clinically meaningful’ response retained with lower dose T-Dxd for HER2-mutated metastatic NSCLC

Author: Lynda Williams


medwireNews: DESTINY-Lung02 trial findings indicate that reducing the dose of trastuzumab deruxtecan (T-DXd) can improve the antibody–drug conjugate’s toxicity profile without loss of activity in patients with previously treated, metastatic HER2-positive non-small-cell lung cancer (NSCLC).

The interim analysis was presented at the ESMO Congress 2022 in Paris, France, by Koichi Goto (National Cancer Center Hospital Easter, Kashiwa, Japan) who said that T-DXd given at 5.4 mg/kg every 3 weeks achieved “clinically meaningful responses” in the phase 2 trial and had a “favorable safety profile” compared with the 6.4 mg/kg dosage.

“The totality of the evidence and a compelling positive benefit–risk balance supported the FDA’s approval of T-DXd 5.4 mg/kg as the first HER2-targeted treatment for patients with previously treated HER2-mutant non-small-cell lung cancer and support the establishment of TdXd as a new standard of care in this population,” the presenter stated.

The study included 152 patients who had received at least platinum-based chemotherapy before being randomly assigned to receive T-DXd 5.4 mg/kg (n=102) or 6.4 mg/kg (n=50) every 3 weeks. But the current data presented were from a prespecified early cohort of 52 patients and 28 patients from the two dosage arms, respectively, who had been followed up for a minimum of 4.5 months and had been assessed three times after study entry, Goto explained.

After an average 5.6 months of follow-up, the objective response rate by blinded independent central review was 53.8% for the patients in the 5.4 mg/kg arm and 42.9% for those given the higher dose; the study was not powered for a statistical comparison.

The corresponding rates of disease control were 90.4% and 92.9%, with median duration unreached in the 5.4 mg/kg arm and 5.9 months for the 6.4 mg/kg arm.

Analysis of data for the safety cohort of all patients who had received at least one T-DXd dose and were followed up for almost 4 months showed that treatment-emergent adverse events (TEAEs) of any grade occurred in most patients whether treated with the 5.4 or 6.5 mg/kg dose (92.1 vs 100%), while grade 3 and more severe TEAEs were reported for 31.7% and 58.0%, respectively.

Patients given T-Dxd at the 5.4 mg/kg dose were less likely than their counterparts given the higher dose to require dose reductions (9.9 vs 26.0%), interruptions (13.9 vs 30.0%), or discontinuation (7.9 vs 16.0%).

Any-grade interstitial lung disease (ILD) was less common with the 5.4 mg/kg than the 6.4 mg/kg regimen (6.0 vs 14.0%) and almost all cases were grade 1 or 2, but Goto emphasized that this AE “remains an important identified risk and effective early detection and management are critical in reducing the severity of ILD.”

In the session discussion, Laura Mezquita (University of Barcelona, Spain) noted that the rate of ILD was lower than the 26% previously reported for the DESTINY-Lung01 study of T-Dxd 6.4 mg/kg.

However, she pointed out that the current study has a shorter duration of follow-up, at 5.4–5.6 months versus 13 months, and therefore “we need longer follow-up to confirm activity” and toxicity.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

ESMO Congress 2022; Paris, France: 9–13 September