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In DESTINY-Breast01 (NCT03248492) and DESTINY-Breast03 (NCT03529110), trastuzumab deruxtecan (T-DXd) demonstrated unprecedented activity in patients (pts) with HER2+ (immunohistochemistry 3+; immunohistochemistry 2+/in situ hybridization+) advanced metastatic breast cancer (mBC), leading to regulatory approvals in several countries for HER2+ unresectable/mBC after a prior anti–HER2-based regimen. DESTINY-Breast02 (NCT03523585) is a phase 3 trial of T-DXd vs treatment of physician’s choice (TPC) in patients with centrally confirmed HER2+ mBC previously treated with trastuzumab emtansine (T-DM1). It acts as a confirmatory study for the pivotal phase 2 DESTINY-Breast01 trial. Here we report the primary results of DESTINY-Breast02. Methods: Pts with HER2+ mBC were randomized 2:1 to receive T-DXd or TPC (trastuzumab + capecitabine or lapatinib + capecitabine) and stratified by hormone receptor (HR) status (HR+/HR-), prior pertuzumab treatment, and history of visceral disease. The primary endpoint of this time-driven primary analysis was progression-free survival (PFS) as determined by blinded independent central review (BICR). The powered secondary endpoint was overall survival (OS). Other secondary endpoints included confirmed objective response rate (ORR) by BICR, duration of response (DoR) by BICR, PFS by investigator assessment, safety, and others. Results: 608 pts were randomized to receive T-DXd (n = 406) or TPC (n = 202). Pts receiving T-DXd and TPC had a median age of 54.2 years (range, 22.4-88.5 years) and 54.7 years (range, 24.7-86.5 years), respectively, with a median of 2 (range, 0-10 and range,1-8) prior lines of systemic therapy (excluding hormone therapy) in the metastatic setting. Median treatment duration was 11.3 mo in the T-DXd arm and ~4.5 mo in the TPC arm. Efficacy and safety results are shown in the table below. T-DXd significantly improved PFS (HR, 0.36; 95% CI, 0.28-0.45; P <0.000001) and OS (HR, 0.66; 95% CI, 0.50-0.86; P = 0.0021) compared with TPC. Confirmed ORR was 69.7% (14% complete response) with T-DXd and 29.2% (5.0% complete response) with TPC. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 52.7% and 44.1% of pts receiving T-DXd and TPC, respectively. Adjudicated drug-related interstitial lung disease (ILD) occurred in 10.4% of pts with T-DXd vs 0.5% of pts with TPC. In pts receiving T-DXd, most ILD cases (88.1%) were grade 1/2 and grade 5 ILD was reported in 2 (0.5%) pts. Conclusions: Results from DESTINY-Breast02 confirmed the clinical benefit and superiority of T-DXd over conventional chemotherapy-based regimens in pts with HER2+ mBC previously treated with T-DM1, as evidenced by significant and clinically meaningful improvements in PFS and OS. These data, together with earlier reported results from the DESTINY-Breast03 study of T-DXd vs T-DM1 solidify T-DXd as an optimal treatment option in pts with progressive HER2+ mBC across broad settings. Editorial Acknowledgment Under guidance of the authors, assistance in medical writing and editorial support was provided by Caylin Bosch, PhD, of ApotheCom, and was funded by Daiichi Sankyo. Funding This study was funded by Daiichi Sankyo and AstraZeneca. Table. Summary of Efficacy and Safety Results for T-DXd and TPC in Patients With HER2+ mBC Previously Treated With T-DM1 Citation Format: Ian Krop, Yeon H. Park, Sung-Bae Kim, Giuliano Borges, Sercan Aksoy, Joaquin Gavila Gregori, Rebecca Roylance, Elgene Lim, Rinat Yerushalmi, Flora Zagouri, Francois P. Duhoux, Tanja Fehm, Toshimi Takano, Anton Egorov, Iris Wu, Jillian Cathcart, Changan Chu, Fabrice Andre. GS2-01 Trastuzumab deruxtecan vs physician’s choice in patients with HER2+ unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine: primary results of the randomized, phase 3 study DESTINY-Breast02 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS2-01.

Background Adults aged 65 years and older represent an increasing proportion of United States (U.S.) tuberculosis (TB) cases, and their clinical complexity creates unique issues for TB management. In Alameda County, California, we examined clinical characteristics and treatment outcomes among older adults with TB disease. Methods We evaluated demographic and clinical surveillance data from all adult TB cases in Alameda County during 2016–2019. We further reviewed public health department charts for TB cases among individuals aged 65 years and older to obtain more detailed information on co-morbidities, adverse effects, and treatment outcomes. Demographics, clinical characteristics, and outcomes were compared in younger adults (15-64) to older adults (≥ 65), who were further stratified by those aged 75 years and older. All comparisons were conducted using Fisher’s exact or Mann-Whitney U tests. Results Of 517 adult TB cases, 172 (33%) were older adults, and more likely to be male (68.6%), Asian (89.0%), non-U.S. born (98.3%), and have diabetes (32.6%) compared to younger adults (Table). At time of TB diagnosis, older adults were more likely than younger adults to have a negative interferon-gamma release assay result (24.6% vs. 16.0%, P=0.01), particularly among aged 75 years and older where 32.9% had a negative result. The majority of older adults with pulmonary TB had sputum smear-negative disease (58.9%) and 19.9% were culture- and polymerase chain reaction assay-negative. On anti-TB treatment, 32.5% of older adults experienced at least one adverse event, most commonly elevated liver enzymes (56.6%) and rash (32.1%). Older adults were more likely to be dead at diagnosis (3.5% vs. 0.0%, P=0.001), and were less likely to complete TB treatment (77.7% vs. 88.4% in younger adults, P=0.002), which was lowest among aged 75 years and older (72.9% vs. 84.3% in those 65-74, P=0.04). Death during treatment was higher in older adults, in particular aged 75 and older compared to 65–74 years (22.9% vs. 7.1%, P=0.01). Conclusion Older adults with TB disease faced several challenges, including negative diagnostic testing and poor treatment outcomes. A greater understanding of the presentation, adverse events and outcomes can guide interventions to improve TB care in this population. Disclosures All Authors: No reported disclosures.