182MO Trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2+ metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1): Updated overall survival (OS) results of the randomized phase III DESTINY-breast (DB-)02 study

DB-02 (NCT03523585) is a randomized, open-label, phase III trial of T-DXd vs TPC in pts previously treated with T-DM1 for HER2+ mBC. At primary study analysis (data cutoff DCO, Jun 30, 2022), T-DXd showed statistically significant improvement in progression-free survival (PFS) and OS vs TPC. We report updated efficacy and safety results (DCO, Sep 29, 2023), including OS. Pts with HER2+ mBC were randomly assigned 2:1 to T-DXd or TPC (trastuzumab + capecitabine cap or lapatinib + cap). This analysis includes OS, PFS, PFS from time of randomization to the progression on next line of therapy or death (PFS2) by investigator, and safety. 608 pts were randomized (T-DXd, n = 406; TPC, n = 202). At DCO, median (range) follow-up (F/U) was 30.2 mo (0.8-60.7) with T-DXd and 20.5 mo (0.0-60.6) with TPC. In the T-DXd and TPC arms, 86.4% and 100% of pts discontinued treatment, respectively; primary reason was progressive disease (47.8%, 73.8%). Median (95% CI) OS was 35.7 mo (30.9-40.8) with T-DXd vs 25.0 mo (20.4-31.5) with TPC. Median PFS2 was 33.0 mo (T-DXd) vs 15.0 mo (TPC). Additional results are in the table. T-DXd was received as poststudy anticancer treatment by 12.9% of pts (32/248) in the T-DXd arm and by 46.6% (69/148) in the TPC arm. Treatment-emergent adverse events (TEAEs) associated with discontinuation occurred in 21.5% of pts with T-DXd and 9.7% with TPC. There were 46 (11.4%) adjudicated drug-related interstitial lung disease/pneumonitis cases with T-DXd; 4 since primary DCO (2 grade 1; 2 grade 2).Table: 182MOUpdated efficacy and safetyT-DXd n = 406TPC n = 202mPFSa (95% CI), mo16.7 (14.7-19.6)5.5 (4.4-6.8)HR (95% CI)0.30 (0.24-0.37)mPFS2a (95% CI), mo33.0 (28.6-36.6)15.0 (13.0-18.1)HR (95% CI)0.42 (0.33-0.53)mOS (95% CI), mo35.7 (30.9-40.8)25.0 (20.4-31.5)HR (95% CI)0.69 (0.55-0.86)Pts with events, n (%)211 (52.0)119 (58.9)24-mo OS rate, % (95% CI)64.6 (59.6-69.2)51.9 (44.4-58.9)36-mo OS rate, % (95% CI)49.2 (44.0-54.3)36.6 (29.5-43.8)T-DXd n = 404TPC n = 195mTreatment duration, mo (range)11.3 (0.7-60.7)∼4.5 (0.1-50.6)Any-grade TEAEs, n (%)403 (99.8)185 (94.9)Grade ≥3 TEAEs, n (%)224 (55.4)87 (44.6)Serious TEAEs, n (%)114 (28.2)46 (23.6)m, median; aBy investigator assessment. Open table in a new tab m, median; aBy investigator assessment. Results reinforce the substantial benefit of T-DXd over TPC in pts with HER2+ mBC previously treated with T-DM1, demonstrated by clinically meaningful improvement in OS, PFS, and PFS2. The safety profile of T-DXd continues to be manageable, with no long-term toxicity observed with longer F/U.