Pooled analysis by best confirmed response to trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ metastatic breast cancer (mBC) from DESTINY-Breast-01, -02, and -03.

1023 Background: DESTINY-Breast (DB)-01, -02, and -03 evaluated T-DXd in pts with HER2+ mBC who received ≥1 prior line of therapy. These studies showed confirmed objective response rates by independent central review (ICR; blinded for DB-02 and -03) of 62%, 70%, and 79% and complete response (CR) rates of 7%, 14%, and 21%, respectively, with T-DXd. We report a pooled analysis according to pts’ best confirmed response in DB-01, -02, or -03. Methods: Endpoints included best confirmed response per (blinded) ICR (BICR) based on RECIST v1.1, duration of response (DoR), progression-free survival (PFS) by (B)ICR, overall survival (OS), and safety. Results: The median (range) duration of T-DXd treatment for pts with a CR, partial response (PR), or stable disease (SD)/progressive disease (PD) was 27.4 (4.5-45.1) mo, 14.0 (2.1-39.3) mo, or 6.2 (0.7-40.1) mo, respectively. Of 834 evaluable pts assigned to T-DXd in DB-01, -02, or -03, 125 (15.0%) had a CR, 477 (57.2%) had a PR, and 232 (27.8%) had SD/PD. Pts with CR had a median of 2 prior regimens (range, 1-11) in the metastatic setting, whereas pts with PR or SD/PD had a median of 3 prior regimens. As shown in the Table, pts with CR had more favorable PFS and OS outcomes vs pts with PR or SD/PD. The proportion of pts with drug-related, serious treatment-emergent adverse events (TEAEs) was numerically lower in pts with CR (8.0%) than those with PR (12.4%) or SD/PD (15.5%). Pts with CR also had numerically lower rates of drug-related TEAEs associated with T-DXd discontinuation (14.4% vs 17.8% or 16.8%) and adjudicated drug-related interstitial lung disease (ILD)/pneumonitis (8.8% 0 fatal vs 15.1% 2 fatal or 11.6% 5 fatal) and longer median time to first ILD onset (461 days vs 211 or 125 days) vs pts with PR or SD/PD. Conclusions: Pts treated with T-DXd benefited from durable responses resulting in prolonged PFS and OS, especially those with a CR. Despite longer treatment duration in responders, safety remained generally manageable and did not result in a higher percentage of pts with TEAEs over time. These results further support the use of T-DXd across broad pt groups with HER2+ mBC. Clinical trial information: NCT03248492 , NCT03523585 , NCT03529110 . Table: see text