First-line (1L) trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-mutant (HER2m) NSCLC: Patient-reported outcomes (PROs) from DESTINY-Lung04 (DL-04)

DESTINY-Lung04

Paciente / Población Intervención / Exposición Comparación Desenlace

In patients with untreated advanced HER2-mutant NSCLC, trastuzumab deruxtecan delayed deterioration in patient-reported cough compared with pembrolizumab plus chemotherapy.

N

454pacientes

Diseño

Global, open-label, phase 3 trial in which patients with treatment-naive advanced or metastatic HER2-mutant (exon 19/20) NSCLC were randomised 1:1 to first-line trastuzumab deruxtecan or pembrolizumab plus platinum chemotherapy and pemetrexed (NCT05048797).

Desenlace

This report covers secondary patient-reported outcome endpoints. The first is time to deterioration on treatment in cough, dyspnoea and chest pain, measured with the NSCLC-SAQ. The second is patient-reported tolerability on treatment: physical function on the EORTC QLQ-C30 PF subscale, overall side-effect bother on the PGI-TT, and symptomatic AEs from the EORTC and PRO-CTCAE item libraries. High side-effect bother over the first 12 weeks was exploratory. The trial's efficacy result was PFS, which is not given in this abstract.

ResultadoMedian time to deterioration in cough 26.2 months (95% CI 17.1-NC) with trastuzumab deruxtecan vs 11.0 months (95% CI 7.4-NC) with pembrolizumab plus chemotherapy; HR 0.66 (95% CI 0.44-0.99). Dyspnoea 10.1 (95% CI 6.5-NC) vs 5.1 (95% CI 3.2-11.0) months; HR 0.77 (95% CI 0.54-1.09). Chest pain NC (95% CI 11.5-NC) vs 14.3 (95% CI 8.3-NC) months; HR 0.80 (95% CI 0.54-1.18). Maintained or improved physical function was similar across arms until Week 18. It was generally higher with trastuzumab deruxtecan from Week 20 and at end of treatment: 66.7% vs 57.7%. High side-effect bother occurred in 13.4% of patient-weeks in each arm. Median treatment duration 12.3 (0.7-44.8) vs 7.1 (0.7-49.1) months.

Novello S, Rotow JK, Tanaka K, et al. Presented at ESMO Congress 2026, abstract LBA74, 24 October. Not yet published.

Discusión y crítica

Patient-reported cough deteriorated later with trastuzumab deruxtecan, but the HR's upper confidence limit of 0.99 only just excludes no effect, and the abstract gives no P values or multiplicity control for these secondary endpoints. The dyspnoea and chest pain HRs have confidence intervals that cross 1. The trastuzumab deruxtecan chest pain median and several upper confidence limits are not estimable. Because the trial was open label, patients knew their treatment, which can bias self-reported symptoms and tolerability. Median treatment duration was much longer with trastuzumab deruxtecan, so on-treatment comparisons from Week 20 and at end of treatment may reflect who remained on therapy, and symptomatic AE data are deferred to the presentation.