Browsing by Author "Tolaney, Sara M."

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    Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab for Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results and Correlative Analyses From ATEMPT
    (Wolters Kluwer, 2024) Tarantino, Paolo; Tayob, Nabihah; Villacampa, Guillermo; Dang, Chau; Yardley, Denise A.; Isakoff, Steven J.; Valero, Vicente; Faggen, Meredith; Mulvey, Therese; Bose, Ron; Weckstein, Douglas; Wolff, Antonio C.; Reeder-Hayes, Katherine; Rugo, Hope S.; Ramaswamy, Bhuvaneswari; Zuckerman, Dan; Hart, Lowell; Gadi, Vijayakrishna K.; Constantine, Michael; Cheng, Kit; Merrill Garrett, Audrey; Marcom, P. Kelly; Albain, Kathy; DeFusco, Patricia; Tung, Nadine; Ardman, Blair; Nanda, Rita; Jankowitz, Rachel C.; Rimawi, Mothaffar; Abramson, Vandana; Pohlmann, Paula R.; Van Poznak, Catherine; Forero-Torres, Andres; Liu, Minetta C.; Ruddy, Kathryn J.; Waks, Adrienne G.; DeMeo, Michelle; Burstein, Harold J.; Partridge, Ann H.; Dell'Orto, Patrizia; Russo, Leila; Krause, Emma; Newhouse, Daniel J.; Kurt, Busem Binboğa; Mittendorf, Elizabeth A.; Schneider, Bryan; Prat, Aleix; Winer, Eric P.; Krop, Ian E.; Tolaney, Sara M.; Consortium of the TBCRC Translational Investigators; TBCRC Translational Investigators; Medicine, School of Medicine
    Purpose: Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need. Methods: In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1. Correlative analyses included the HER2DX genomic tool, multiomic evaluations of HER2 heterogeneity, and predictors of thrombocytopenia. Results: After a median follow-up of 5.8 years, 11 iDFS events were observed in the T-DM1 arm, consistent with a 5-year iDFS of 97.0% (95% CI, 95.2 to 98.7). At 5 years, the recurrence-free interval (RFI) was 98.3% (95% CI, 97.0 to 99.7), the overall survival was 97.8% (95% CI, 96.3 to 99.3), and the breast cancer-specific survival was 99.4% (95% CI, 98.6 to 100). Comparable iDFS was observed with T-DM1 irrespective of tumor size, hormone receptor status, centrally determined HER2 immunohistochemical score, and receipt of T-DM1 for more or less than 6 months. Although ATEMPT was not powered for this end point, the 5-year iDFS in the TH arm was 91.1%. Among patients with sufficient tissue for HER2DX testing (n = 187), 5-year outcomes significantly differed according to HER2DX risk score, with better RFI (98.1% v 81.8%, hazard ratio [HR], 0.10, P = .01) and iDFS (96.3% v 81.8%, HR, 0.20, P = .047) among patients with HER2DX low-risk versus high-risk tumors, respectively. Conclusion: Adjuvant T-DM1 for 1 year leads to outstanding long-term outcomes for patients with stage I HER2-positive breast cancer. A high HER2DX risk score predicted a higher risk of recurrence in ATEMPT.
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    Cardiac Outcomes of Patients Receiving Adjuvant Weekly Paclitaxel and Trastuzumab for Node-Negative, ERBB2-Positive Breast Cancer
    (American Medical Association, 2016-01) Dang, Chau; Guo, Hao; Najita, Julie; Yardley, Denise; Marcom, Kelly; Albain, Kathy; Rugo, Hope; Miller, Kathy; Ellis, Matthew; Shapira, Iuliana; Wolff, Antonio C.; Carey, Lisa A.; Moy, Beverly; Groarke, John; Moslehi, Javid; Krop, Ian; Burstein, Harold J.; Hudis, Clifford; Winer, Eric P.; Tolaney, Sara M.; Department of Medicine, IU School of Medicine
    IMPORTANCE: Trastuzumab is a life-saving therapy but is associated with symptomatic and asymptomatic left ventricular ejection fraction (LVEF) decline. We report the cardiac toxic effects of a nonanthracycline and trastuzumab-based treatment for patients with early-stage human epidermal growth factor receptor 2 (ERBB2, formerly HER2 or HER2/neu)-positive breast cancer. OBJECTIVE: To determine the cardiac safety of paclitaxel with trastuzumab and the utility of LVEF monitoring in patients with node-negative, ERBB2-positive breast cancer. DESIGN, SETTING, AND PARTICIPANTS: In this secondary analysis of an uncontrolled, single group study across 14 medical centers, enrollment of 406 patients with node-negative, ERBB2-positive breast cancer 3 cm, or smaller, and baseline LVEF of greater than or equal to 50% occurred from October 9, 2007, to September 3, 2010. Patients with a micrometastasis in a lymph node were later allowed with a study amendment. Median patient age was 55 years, 118 (29%) had hypertension, and 30 (7%) had diabetes. Patients received adjuvant paclitaxel for 12 weeks with trastuzumab, and trastuzumab was continued for 1 year. Median follow-up was 4 years. INTERVENTIONS: Treatment consisted of weekly 80-mg/m2 doses of paclitaxel administered concurrently with trastuzumab intravenously for 12 weeks, followed by trastuzumab monotherapy for 39 weeks. During the monotherapy phase, trastuzumab could be administered weekly 2-mg/kg or every 3 weeks as 6-mg/kg. Radiation and hormone therapy were administered per standard guidelines after completion of the 12 weeks of chemotherapy. Patient LVEF was assessed at baseline, 12 weeks, 6 months, and 1 year. MAIN OUTCOMES AND MEASURES: Cardiac safety data, including grade 3 to 4 left ventricular systolic dysfunction (LVSD) and significant asymptomatic LVEF decline, as defined by our study, were reported. RESULTS: Overall, 2 patients (0.5%) (95% CI, 0.1%-1.8%) developed grade 3 LVSD and came off study, and 13 (3.2%) (95% CI, 1.9%-5.4%) had significant asymptomatic LVEF decline, 11 of whom completed study treatment. Median LVEF at baseline was 65%; 12 weeks, 64%; 6 months, 64%; and 1 year, 64%. CONCLUSIONS AND RELEVANCE: Cardiac toxic effects from paclitaxel with trastuzumab, manifesting as grade 3 or 4 LVSD or asymptomatic LVEF decline, were low. Patient LVEF was assessed at baseline, 12 weeks, 6 months, and 1 year, and our findings suggest that LVEF monitoring during trastuzumab therapy without anthracyclines could be simplified for many individuals.
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    Cardiac outcomes of subjects on adjuvant trastuzumab emtansine vs paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT) study (TBCRC033): a randomized controlled trial
    (Springer Nature, 2022-02-16) Barroso-Sousa, Romualdo; Tarantino, Paolo; Tayob, Nabihah; Dang, Chau; Yardley, Denise A.; Isakoff, Steven J.; Valero, Vicente; Faggen, Meredith; Mulvey, Therese; Bose, Ron; Hu, Jiani; Weckstein, Douglas; Wolff, Antonio C.; Reeder-Hayes, Katherine; Rugo, Hope S.; Ramaswamy, Bhuvaneswari; Zuckerman, Dan; Hart, Lowell; Gadi, Vijayakrishna K.; Constantine, Michael; Cheng, Kit; Briccetti, Frederick; Schneider, Bryan; Merrill Garrett, Audrey; Marcom, Kelly; Albain, Kathy; DeFusco, Patricia; Tung, Nadine; Ardman, Blair; Nanda, Rita; Jankowitz, Rachel C.; Rimawi, Mothaffar; Abramson, Vandana; Pohlmann, Paula R.; Van Poznak, Catherine; Forero-Torres, Andres; Liu, Minetta; Ruddy, Kathryn J.; Zheng, Yue; Rosenberg, Shoshana M.; Gelber, Richard D.; Trippa, Lorenzo; Barry, William; DeMeo, Michelle; Burstein, Harold; Partridge, Ann; Winer, Eric P.; Krop, Ian; Tolaney, Sara M.; Medicine, School of Medicine
    The excellent outcomes seen in patients treated with adjuvant trastuzumab emtansine (T-DM1) in the ATEMPT trial and the favorable toxicity profile associated with this agent make T-DM1 a potential therapeutic option for select patients with stage I HER2-positive breast cancer. Moreover, T-DM1 is an established adjuvant treatment for patients with HER2-positive breast cancer with the residual invasive disease after neoadjuvant therapy. Given that cardiotoxicity is the most significant adverse event of trastuzumab, which is a main molecular component of T-DM1, we conducted a sub-analysis of the ATEMPT trial to determine the cardiac safety of adjuvant T-DM1. In this analysis, the incidence of grade 3-4 left ventricular systolic dysfunction (LVSD) in T-DM1 or trastuzumab plus paclitaxel arms were respectively 0.8 and 1.8%. In addition, three (0.8%) patients in the T-DM1 arm and six (5.3%) patients in the adjuvant paclitaxel with trastuzumab (TH) arm experienced a significant asymptomatic left ventricular ejection fraction (LVEF) decline that per-protocol required holding T-DM1 or trastuzumab. All patients with available follow-up data experienced full resolution of cardiac symptoms and LVEF normalization. Furthermore, we performed an exploratory analysis to assess the relationship between age, baseline LVEF, and body mass index with cardiac outcomes. No significant association between these baseline characteristics and the incidence of significant asymptomatic LVEF decline or symptomatic LVSD was identified. The low incidence of significant cardiac adverse events in this population during therapy with adjuvant T-DM1 suggests that studies on the cost-effectiveness of cardiac monitoring during adjuvant therapy using anthracycline-free regimens are needed.