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T-DXd, an approved therapy for multiple cancers, carries a risk of interstitial lung disease/pneumonitis (ILD) which may have fatal outcomes if not appropriately identified and managed. Management guidelines require interrupting T-DXd for all ILD grades, even if asymptomatic, but patients (pts) with Gr 1 ILD may be retreated upon complete radiographic recovery. In this retrospective analysis of T-DXd trials, we examined RTx duration and recurrence of ILD (rILD). Data were pooled from 9 clinical trials of pts with HER2-altered breast, gastric, colorectal, and non-small cell lung cancer who received ≥1 dose of T-DXd (5.4-8.0 mg/kg) monotherapy. T-DXd RTx duration and rILD were assessed in pts following Gr 1 first ILD (fILD); defined as complete recovery from investigator (inv)-assessed Gr 1 drug-related ILD, confirmed by an independent adjudication committee (AC). Overall, 9.0% (193/2145) of pooled pts had Gr 1 fILD, 50.3% (97/193) of whom received steroids. Per inv assessment or treatment dose discontinuation requirements (per protocol/label), 76.7% (148/193) of Gr 1 fILD pts were not eligible for T-DXd RTx. Following Gr 1 fILD, 23.3% (45/193) of pts were retreated with T-DXd. Median RTx duration was 85 d (range, 1-848 d); 31.1% (14/45) of pts were retreated with a 1-level reduced dose vs their original T-DXd dose; 17.8% (8/45) received T-DXd RTx for ≥1 year. Of those retreated: 2 pts (4.4% 2/45) had RTx before Gr 1 fILD was confirmed resolved, per AC, and events progressed to Gr 2 and Gr 3 (1 each), and 33.3% (15/45) had rILD (median time to rILD was 64 d range, 22-391 d). All pts with rILD received the same T-DXd dose level as their original dose: 40.0% (6/15) of rILD events were AC-assessed ILD Gr 1; 60.0% (9/15) Gr 2; no Gr ≥3 events. At the data cutoff from each trial, per inv assessment, 20.0% (3/15) of rILD cases were ongoing; 53.3% (8/15) of pts recovered without sequalae; 6.7% (1/15) recovered with sequalae; 20.0% (3/15) did not recover. This is the first pooled analysis of T-DXd RTx data after Gr 1 fILD recovery which shows clinically meaningful extension of treatment duration with RTx. All rILD events were of low grade and generally manageable using existing treatment guidelines.
Rugo et al. (Wed,) studied this question.