No abstract

Metastatic breast cancer is a heterogeneous disease that presents in varying forms, and a growing number of therapeutic options makes it difficult to determine the best choice in each particular situation. When selecting a systemic treatment, it is important to consider the medication administered in the previous stages, such as acquired resistance, type of progression, time to relapse, tumor aggressiveness, age, comorbidities, pre-and post-menopausal status, and patient preferences. Moreover, tumor genomic signatures can identify different subtypes, which can be used to create patient profiles and design specific therapies. However, there is no consensus regarding the best treatment sequence for each subgroup of patients. During the SABCC Congress of 2014, specialized breast cancer oncologists from referral hospitals in Europe met to define patient profiles and to determine specific treatment sequences for each one. Conclusions were then debated in a final meeting in which a relative degree of consensus for each treatment sequence was established. Four patient profiles were defined according to established breast cancer phenotypes: pre-menopausal patients with luminal subtype, post-menopausal patients with luminal subtype, patients with triple-negative subtype, and patients with HER2-positive subtype. A treatment sequence was then defined, consisting of hormonal therapy with tamoxifen, aromatase inhibitors, fulvestrant, and mTOR inhibitors for pre-and post-menopausal patients; a chemotherapy sequence for the first, second, and further lines for luminal and triple-negative patients; and an optimal sequence for treatment with new antiHER2 therapies. Finally, a document detailing all treatment sequences, that had the agreement of all the oncologists, was drawn up as a guideline and advocacy tool for professionals treating patients with this disease.

No abstract

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.

Although the metastasic breast cancer is still an incurable disease, recent advances have increased significantly the time to progression and the overall survival. However, too much information has been produced in the last 2 years, so a well-based guideline is a valuable document in treatment decision making. The SEOM guidelines are intended to make evidence-based recommendations on how to manage patients with advanced and recurrent breast cancer to achieve the best patient outcomes based on a rational use of the currently available therapies. To assign a level of certainty and a grade of recommendation the United States Preventive Services Task Force guidelines methodology was selected as reference.