Browsing by Author "Valero, Vicente"

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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 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.
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    Updated Results of TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathological Complete Response to Pertuzumab and Trastuzumab in Breast Cancer
    (American Society of Clinical Oncology, 2021) Connolly, Roisin M.; Leal, Jeffrey P.; Solnes, Lilja; Huang, Chiung-Yu; Carpenter, Ashley; Gaffney, Katy; Abramson, Vandana; Carey, Lisa A.; Liu, Minetta C.; Rimawi, Mothaffar; Specht, Jennifer; Storniolo, Anna Maria; Valero, Vicente; Vaklavas, Christos; Krop, Ian E.; Winer, Eric P.; Camp, Melissa; Miller, Robert S.; Wolff, Antonio C.; Cimino-Mathews, Ashley; Park, Ben H.; Wahl, Richard L.; Stearns, Vered; Medicine, School of Medicine
    Purpose: Predictive biomarkers to identify patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who may benefit from targeted therapy alone are required. We hypothesized that early measurements of tumor maximum standardized uptake value corrected for lean body mass (SULmax) on 18F-labeled fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) would predict pathologic complete response (pCR) to pertuzumab and trastuzumab (PT). Patients and methods: Patients with stage II or III, estrogen receptor-negative, HER2-positive breast cancer received four cycles of neoadjuvant PT. 18F-labeled fluorodeoxyglucose positron emission tomography-computed tomography was performed at baseline and 15 days after PT initiation (C1D15). Eighty evaluable patients were required to test the null hypothesis that the area under the curve of percent change in SULmax by C1D15 predicting pCR is ≤ 0.65, with a one-sided type I error rate of 10%. Results: Eighty-eight women were enrolled (83 evaluable), and 85% (75 of 88) completed all four cycles of PT. pCR after PT alone was 22%. Receiver operator characteristic analysis of percent change in SULmax by C1D15 yielded an area under the curve of 0.72 (80% CI, 0.64 to 0.80; one-sided P = .12), which did not reject the null hypothesis. However, between patients who obtained pCR and who did not, a significant difference in median percent reduction in SULmax by C1D15 was observed (63.8% v 41.8%; P = .004) and SULmax reduction ≥ 40% was more prevalent (83% v 52%; P = .03; positive predictive value, 31%). Participants not obtaining a 40% reduction in SULmax by C1D15 were unlikely to obtain pCR (negative predictive value, 91%). Conclusion: Although the primary objective was not met, early changes in SULmax predict response to PT in estrogen receptor-negative and HER2-positive breast cancer. Once optimized, this quantitative imaging strategy may facilitate tailoring of therapy in this setting.