Dr Geyer on ILD and Radiation Pneumonitis Data With T-DXd in DESTINY-Breast05

“There does not appear to be a clear advantage to either the sequential [radiation] approach or the concurrent approach.”

Charles E. Geyer, MD, division chief of Malignant Hematology and Medical Oncology in the Department of Medicine at the University of Pittsburgh School of Medicine and a breast medical oncologist at the University of Pittsburgh Medical Center (UPMC) Magee Womens Hospital at the UPMC Hillman Cancer Center, discussed findings from a secondary safety analysis of the phase 3 DESTINY-Breast05 trial (NCT04622319) evaluating interstitial lung disease (ILD) and radiation pneumonitis incidence by adjuvant radiotherapy timing in patients treated with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) or ado-trastuzumab emtansine (T-DM1; Kadcyla).

DESTINY-Breast05 established the efficacy of T-DXd over T-DM1 in patients with high-risk HER2-positive early breast cancer and residual invasive disease after neoadjuvant therapy. In the trial, radiotherapy could be initiated concurrently with study treatment or completed sequentially beforehand, which allowed this analysis to compare pulmonary outcomes by adjuvant radiotherapy timing, according to Geyer.

Among T-DXd–treated patients, ILD developed in 42 (9.6%) with the concurrent approach and 34 (10.7%) with the sequential approach, Geyer said. Since more patients were treated concurrently than sequentially, the percentages are the relevant comparison, he emphasized; on that basis, the rates were similar between the arms, with no statistical difference of any magnitude and no clinically important difference, he noted.

Of the 42 concurrent ILD cases, 29 patients recovered, 5 were improving but still had some changes, 7 had not recovered, and 1 died, Geyer said. Among the 34 sequential cases, the figures were similar: 20 patients recovered, 5 were recovering, 8 had not recovered, and 1 died. Most patients had recovered or were on their way to recovering at the last data cutoff, with no substantial difference between the 2 approaches, he noted.

The median duration of ILD was 77.0 days with the sequential approach and 67.0 days with the concurrent approach, Geyer said, again indicating no clear advantage to either strategy.

Regarding efficacy based on radiation timing, there was no statistical difference between the 2 approaches, though Geyer said the numerical difference between the HRs was of interest. Ultimately, the data show that either approach is reasonable, according to Geyer.

The trial also identified how often patients had asymptomatic radiation pneumonitis. Symptomatic radiation pneumonitis rates in the trial were low, but because the analysis captured events in both T-DM1– and T-DXd–treated patients, any-grade data were available and of interest, Geyer said. With the sequential approach, the rate of any-grade radiation pneumonitis was 34.5% with T-DXd and 37.4% with T-DM1; with the concurrent approach, the rates were lower, at 29.2% and 26.7%, respectively. Reassuringly, there did not appear to be higher levels of grade 1 radiation pneumonitis in patients who received T-DXd vs T-DM1, he concluded.

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