19 results on '"Sparano, Joseph A"'
Search Results
2. ECOG-ACRIN EAZ171: Prospective validation trial of germline variants and taxane type in association with taxane-induced peripheral neuropathy (TIPN) in Black women with early-stage breast cancer.
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Ballinger, Tarah Jean, primary, Zhao, Fengmin, additional, Sparano, Joseph A., additional, Garcia, Sofia F., additional, Shen, Fei, additional, Virani, Shamsuddin, additional, Srinivasiah, Jayanthi, additional, Stringer-Reasor, Erica Michelle, additional, Chitalia, Ami, additional, Davis, Andrew A., additional, Makower, Della F., additional, Incorvati, Jason, additional, Simon, Melissa A., additional, Mitchell, Edith P., additional, DeMichele, Angela, additional, Miller, Kathy, additional, Wagner, Lynne I., additional, Wolff, Antonio C., additional, and Schneider, Bryan P., additional
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- 2024
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3. Phase II study of a PARP inhibitor, talazoparib, in HER2- metastatic breast cancer (MBC) with a somatic BRCA1/2mutation identified in a cell-free DNA or tumor tissue genotyping assay.
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Vidula, Neelima, primary, Damodaran, Senthil, additional, Bhave, Manali A., additional, Blouch, Erica, additional, Ogbenna, Ogadinma, additional, Flaum, Lisa E., additional, Shah, Ami N., additional, Abramson, Vandana G, additional, Cristofanilli, Massimo, additional, Sparano, Joseph A., additional, Ostrer, Harry, additional, Horick, Nora K., additional, Rugo, Hope S., additional, and Bardia, Aditya, additional
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- 2024
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4. Impact of race/ethnicity on the MammaPrint genomic assay risk and prognosis in early breast cancer (EBC): A National Cancer Database (NCDB) analysis.
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Patel, Rima, primary, Sheng, Tianxiang, additional, Diniz, Marcio A., additional, Sparano, Joseph A., additional, and Tiersten, Amy, additional
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- 2024
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5. Clinical and Genomic Risk for Late Breast Cancer Recurrence and Survival.
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Sparano, Joseph A., Crager, Michael, Gray, Robert J., Tang, Gong, Hoag, Jess, Baehner, Frederick L., Shak, Steven, Makower, Della F., Albain, Kathy S., Hayes, Daniel F., Geyer Jr., Charles E., Dees, Elizabeth C., Goetz, Matthew P., Olson Jr., John A., Lively, Tracy, Badve, Sunil S., Saphner, Thomas J., Whelan, Timothy J., Kaklamani, Virginia G., and Wolmark, Norman
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BREAST cancer prognosis ,RISK assessment ,BIOLOGICAL models ,CANCER relapse ,GENOMICS ,BREAST tumors ,CHI-squared test ,DESCRIPTIVE statistics ,LONGITUDINAL method ,SURVIVAL analysis (Biometry) ,TUMOR classification ,COMPARATIVE studies ,CONFIDENCE intervals ,PROPORTIONAL hazards models ,OVERALL survival ,DISEASE risk factors - Abstract
Background: The 21-gene recurrence score (RS) assay (Oncotype DX) is used to guide adjuvant chemotherapy use for patients with hormone receptor-positive, HER2 (human epidermal growth factor receptor 2)-negative, axillary node-negative breast cancer. Its role, however, in providing prognostic information for late distant recurrence when added to clinicopathologic prognostic factors is unknown. Methods: A patient-specific meta-analysis including 10,004 women enrolled in three trials was updated using extended follow-up data from TAILORx, integrating the RS with histologic grade, tumor size, and age at surgery for the RSClin tool. Cox models integrating clinicopathologic factors and the RS were compared by using likelihood ratio (LR) tests. External validation of prognosis for distant recurrence in years 0 to 10 and 5 to 10 was performed in an independent cohort of 1098 women in a real-world registry. Results: RSClin provided significantly more prognostic information than either the clinicopathologic factors (ΔLR chi-square, 86.2; P<0.001) or RS alone (ΔLR chi-square, 131.0; P<0.001). The model was prognostic in an independent cohort for distant recurrence by 10 years after diagnosis (standardized hazard ratio, 1.56; 95% confidence interval, 1.25 to 1.94), was associated with late distant recurrence risk between 5 and 10 years after diagnosis (standardized hazard ratio, 1.78; 95% confidence interval, 1.25 to 2.55), and approximated the observed 10-year distant recurrence risk (Lin concordance, 0.87) and 5- to 10-year distant recurrence risk (Lin concordance, 0.92). Conclusions: The 21-gene RS is prognostic for distant recurrence and overall survival in early breast cancer. A model integrating the 21-gene RS and clinicopathologic factors improved estimates of distant recurrence risk compared with either used individually and stratified late distant recurrence risk. (Funded by the National Cancer Institute, National Institutes of Health [U10CA180820, U10CA180794, UG1CA189859, U10CA180868, and U10CA180822] and others.) [ABSTRACT FROM AUTHOR]
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- 2024
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6. A Case of Hand-Foot Skin Reaction-like Eruption Associated with Pembrolizumab
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Young, Jade, primary, Eversman, Anna, additional, Poplausky, Dina, additional, Suemitsu, Yamato, additional, Niedt, George, additional, Galsky, Matthew, additional, Sparano, Joseph, additional, and Gulati, Nicholas, additional
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- 2024
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7. Lumpectomy without radiation for ductal carcinoma in situ of the breast: 20-year results from the ECOG-ACRIN E5194 study
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Wright, Jean L., primary, Gray, Robert, additional, Rahbar, Habib, additional, Comstock, Christopher E., additional, Tjoe, Judy A., additional, Badve, Sunil, additional, Recht, Abram, additional, Sparano, Joseph A., additional, Davidson, Nancy E., additional, and Wolff, Antonio C., additional
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- 2024
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8. Adjuvant platinum versus capecitabine for residual, invasive, triple‐negative breast cancer: Patient‐reported outcomes in ECOG‐ACRIN EA1131
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Smith, Karen L., primary, Zhao, Fengmin, additional, Mayer, Ingrid A., additional, Tevaarwerk, Amye J., additional, Garcia, Sofia F., additional, Arteaga, Carlos L., additional, Symmans, William F., additional, Park, Ben H., additional, Burnette, Brian L., additional, Makower, Della F., additional, Block, Margaret, additional, Morley, Kimberly A., additional, Jani, Chirag R., additional, Mescher, Craig, additional, Dewani, Shabana J., additional, Brown‐Glaberman, Ursa, additional, Flaum, Lisa E., additional, Mayer, Erica L., additional, Sikov, William M., additional, Rodler, Eve T., additional, DeMichele, Angela M., additional, Sparano, Joseph A., additional, Wolff, Antonio C., additional, Miller, Kathy D., additional, and Wagner, Lynne I., additional
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- 2024
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9. Data from A Phase I/II Study of GSK525762 Combined with Fulvestrant in Patients with Hormone Receptor–positive/HER2-negative Advanced or Metastatic Breast Cancer
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Cescon, David W., primary, Hilton, John, primary, Morales Murilo, Serafin, primary, Layman, Rachel M., primary, Pluard, Timothy, primary, Yeo, Belinda, primary, Park, In Hae, primary, Provencher, Louise, primary, Kim, Sung-Bae, primary, Im, Young-Hyuck, primary, Wyce, Anastasia, primary, Krishnatry, Anu Shilpa, primary, Hicks, Kirsty, primary, Zhang, Qu, primary, Barbash, Olena, primary, Khaled, Ahmed, primary, Horner, Thierry, primary, Dhar, Arindam, primary, Oliveira, Mafalda, primary, and Sparano, Joseph A., primary
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- 2024
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10. Supplementary Data1 from A Phase I/II Study of GSK525762 Combined with Fulvestrant in Patients with Hormone Receptor–positive/HER2-negative Advanced or Metastatic Breast Cancer
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Cescon, David W., primary, Hilton, John, primary, Morales Murilo, Serafin, primary, Layman, Rachel M., primary, Pluard, Timothy, primary, Yeo, Belinda, primary, Park, In Hae, primary, Provencher, Louise, primary, Kim, Sung-Bae, primary, Im, Young-Hyuck, primary, Wyce, Anastasia, primary, Krishnatry, Anu Shilpa, primary, Hicks, Kirsty, primary, Zhang, Qu, primary, Barbash, Olena, primary, Khaled, Ahmed, primary, Horner, Thierry, primary, Dhar, Arindam, primary, Oliveira, Mafalda, primary, and Sparano, Joseph A., primary
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- 2024
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11. Assessment of the safety of nivolumab in people living with HIV with advanced cancer on antiretroviral therapy: the AIDS Malignancy Consortium 095 Study.
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Rajdev, Lakshmi, Jackie Wang, Chia‐Ching, Joshi, Himanshu, Lensing, Shelly, Lee, Jeannette, Ramos, Juan Carlos, Baiocchi, Robert, Ratner, Lee, Rubinstein, Paul G., Ambinder, Richard, Henry, David, Streicher, Howard, Little, Richard F., Chiao, Elizabeth, Dittmer, Dirk P., Einstein, Mark H., Cesarman, Ethel, Mitsuyasu, Ronald, and Sparano, Joseph A.
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HIV-positive persons ,ANTIRETROVIRAL agents ,NIVOLUMAB ,CANCER treatment ,IMMUNE reconstitution inflammatory syndrome ,CD4 lymphocyte count - Abstract
Background: Although immunotherapy has emerged as a therapeutic strategy for many cancers, there are limited studies establishing the safety and efficacy in people living with HIV (PLWH) and cancer. Methods: PLWH and solid tumors or Kaposi sarcoma (KS) receiving antiretroviral therapy and a suppressed HIV viral load received nivolumab at 3 mg/kg every 2 weeks, in two dose deescalation cohorts stratified by CD4 count (stratum 1: CD4 count > 200/µL and stratum 2: CD4 count 100–199/µL). An expansion cohort of 24 participants with a CD4 count > 200/µL was then enrolled. Results: A total of 36 PLWH received nivolumab, including 15 with KS and 21 with a variety of other solid tumors. None of the first 12 participants had dose‐limiting toxicity in both CD4 strata, and five patients (14%) overall had grade 3 or higher immune related adverse events. Objective partial response occurred in nine PLWH and cancer (25%), including in six of 15 with KS (40%; 95% CI, 16.3–64.7). The median duration of response was 9.0 months overall and 12.5 months in KS. Responses were observed regardless of PDL1 expression. There were no significant changes in CD4 count or HIV viral load. Conclusions: Nivolumab has a safety profile in PLWH similar to HIV‐negative subjects with cancer, and also efficacy in KS. Plasma HIV remained suppressed and CD4 counts remained stable during treatment and antiretroviral therapy, indicating no adverse impact on immune function. Trial Registration: ClinicalTrials.gov Identifier: NCT02408861. The anti‐PD1 inhibitor nivolumab may be used safely for treatment of cancer, and has activity in Kaposi sarcoma, in people living with HIV receiving antiretroviral therapy, a suppressed HIV viral load, and CD4 lymphocyte count of at least 100/µL. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Importance of Low- and Moderate-Grade Adverse Events in Patients' Treatment Experience and Treatment Discontinuation: An Analysis of the E1912 Trial.
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O'Connell, Nathaniel S., Zhao, Fengmin, Lee, Ju-Whei, Ip, Edward H., Peipert, John Devin, Graham, Noah, Smith, Mary Lou, Gareen, Ilana F., Carlos, Ruth C., Obeng-Gyasi, Samilia, Sparano, Joseph A., Shanafelt, Tait D., Thomas, Mary L., Cella, David, Wagner, Lynne I., and Gray, Robert
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- 2024
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13. Contributors
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Adesoye, Taiwo, Aebi, Stefan, Aizer, Ayal, Allweis, Tanir M., Arnold, Alicia Huff, Ashfaq, Raheela, Barrio, Andrea V., Bazan, Jose G., Bedrosian, Isabelle, Berkowitz, Alyssa, Bland, Kirby I., Aydi, Zeynep B., Braunstein, Lior Z., Brufsky, Adam, Cahlon, Oren, Carlson, Kjirsten A., Cass, Samuel, Cathcart-Rake, Elizabeth, Caudle, Abigail, Chen, Zhengshan, Chen, Chien, Childs, Daniel S., Chung, Alice, Cody, Hiram S., III, Coleman, Robert, Copeland, Edward M., III, Cox, Solange E., Cox, Dawn M., Czyz, Rebecca, David, Bre Ana, Degnim, Amy C., Dhakal, Ajay, Dietz, Jill R., Esgueva, Antonio J., Euhus, David M., Farr, Deborah E., Fayanju, Oluwadamilola M., Freedman, Gary M., Gallagher, Kristalyn K., Garvey, Patrick Bryan, Gass, Jennifer S., Geletzke, Abby K., Gemignani, Mary L., Giuliano, Armando E., Goldman, Kara N., Golshan, Mehra, Goodman, Chelain R., Gradishar, William J., Greenberg, Caprice C., Grobmyer, Stephen R., Grubstein, Ahuva, Gutnik, Lily, Harris, Eleanor E., Howard, Frederick M., Hunt, Kelly K., Jhawar, Sachin R., Jungheim, Emily S., Kaklamani, Virginia, Kalliath, Naomi J., Karuturi, Meghan S., Kass, Rena B., Khan, Seema A., Khan, Maryam I., Khan, Sadia, Suzanne Klimberg, V., Korourian, Soheila, Krishnamurthy, Jairam, Kuerer, Henry M., Kumarapeli, Asangi R., Kumbla, Pallavi A., Kumthekar, Priya, Lathrop, Kate I., Lee, Anne E., Marilyn Leitch, A., Liang, Diana, Lin, Nancy U., Linda Bi, Wenya, Lippe, Caroline E., Lu, Janice, Lustberg, Maryam, Ma, Emily, Ma, Yanling, Della Makower, Mallory, Melissa Anne, Mancino, Anne Thompson, Massoll, Nicole, Matalkah, Ahmad M., Matar, Regina, Mathew, Aju, McCormick, Beryl, McGuire, Kandace P., Mehra, Karishma, Mendez, Jane E., Menes, Tehillah, Merajver, Sofia D., Mhatre, Priya V., Mitchell, Sunny D., Morikawa, Aki, Muesse, Jason L., Nanda, Rita, Okoro, Stanley, O'Regan, Ruth M., Osipo, Clodia, Pariser, Ashley, Pastoriza, Jessica, Patel, Vijay, Pernas, Sonia, Piltin, Mara A., Pisano, Courtney E., Podoll, Mirna B., Post, Ginell R., Prati, Raquel, Press, Michael F., Pusztai, Lajos, Racz, Jennifer, Rivere, Amy E., Robinson, Angelica S., Rosenbloom, Arlan L., Rosso, Kelly J., Rozenblit, Mariya, Rubio, Isabel T., Ruddy, Kathryn J., Sanders, Melinda E., Sanft, Tara, Savalia, Nirav B., Schuetz, Steven J., Sener, Stephen F., Shah, Ami N., Shahpar, Samman, Shalin, Sara C., Siddiq, Namrah, Silverstein, Melvin J., Simpson, Ashley, Singhal, Dhruv, Smith, Benjamin D., Smith, Karen Lisa, Spanheimer, Philip M., Sparano, Joseph A., Spiguel, Lisa R.P., Stearns, Vered, Steliga, Matthew A., Sun, Susie X., Tarantino, Paolo, Tolaney, Sara M., De La Torre, Jorge I., Tsai, Jacqueline, Valente, Stephanie A., Sorice-Virk, Sarah, Vogel, Victor G., Wapnir, Irene L., Weiser, Roi, Yaney, Alex, Yellala, Amulya, and Zanfagnin, Valentina
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- 2024
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14. 3 - Important Trials of the Last Decade
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Makower, Della and Sparano, Joseph A.
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- 2024
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15. Human Immunodeficiency Virus/AIDS, Human Papillomavirus, and Anal Cancer
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Wang, Chia-ching J., Sparano, Joseph, and Palefsky, Joel M.
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Anal cancer is an increasingly common non–AIDS-defining cancer among individuals infected with the human immunodeficiency virus (HIV). It is associated with human papillomavirus (HPV). HPV16 is the most common genotype detected in anal cancers. The HPV types detected in anal cancer are included in the 9-valent vaccine. HPV vaccines have demonstrated efficacy in reducing anal precancerous lesions in HIV-infected individuals. Standard treatment has been fluorouracil and mitomycin (or cisplatin) plus radiation. Continued studies are needed to test new treatment strategies in HIV-infected patients with anal cancer to determine which treatment protocols provide the best therapeutic index.
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- 2024
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16. ECOG-ACRIN EAZ171: Prospective Validation Trial of Germline Predictors of Taxane-Induced Peripheral Neuropathy in Black Women With Early-Stage Breast Cancer.
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Schneider BP, Zhao F, Ballinger TJ, Garcia SF, Shen F, Virani S, Cella D, Bales C, Jiang G, Hayes L, Miller N, Srinivasiah J, Stringer-Reasor EM, Chitalia A, Davis AA, Makower DF, Incorvati J, Simon MA, Mitchell EP, DeMichele A, Miller KD, Sparano JA, Wagner LI, and Wolff AC
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- Humans, Female, Middle Aged, Prospective Studies, Adult, Aged, Taxoids adverse effects, Taxoids administration & dosage, Neoplasm Staging, Germ-Line Mutation, Bridged-Ring Compounds adverse effects, Bridged-Ring Compounds administration & dosage, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Peripheral Nervous System Diseases chemically induced, Peripheral Nervous System Diseases genetics, Paclitaxel administration & dosage, Paclitaxel adverse effects, Docetaxel administration & dosage, Docetaxel adverse effects, Black or African American genetics
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Purpose: Black women experience higher rates of taxane-induced peripheral neuropathy (TIPN) compared with White women when receiving adjuvant once weekly paclitaxel for early-stage breast cancer, leading to more dose reductions and higher recurrence rates. EAZ171 aimed to prospectively validate germline predictors of TIPN and compare rates of TIPN and dose reductions in Black women receiving (neo)adjuvant once weekly paclitaxel and once every 3 weeks docetaxel for early-stage breast cancer., Methods: Women with early-stage breast cancer who self-identified as Black and had intended to receive (neo)adjuvant once weekly paclitaxel or once every 3 weeks docetaxel were eligible, with planned accrual to 120 patients in each arm. Genotyping was performed to determine germline neuropathy risk. Grade 2-4 TIPN by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 was compared between high- versus low-risk genotypes and between once weekly paclitaxel versus once every 3 weeks docetaxel within 1 year. Patient-rated TIPN and patient-reported outcomes were compared using patient-reported outcome (PRO)-CTCAE and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity., Results: Two hundred and forty of 249 enrolled patients had genotype data, and 91 of 117 (77.8%) receiving once weekly paclitaxel and 87 of 118 (73.7%) receiving once every 3 weeks docetaxel were classified as high-risk. Physician-reported grade 2-4 TIPN was not significantly different in high- versus low-risk genotype groups with once weekly paclitaxel (47% v 35%; P = .27) or with once every 3 weeks docetaxel (28% v 19%; P = .47). Grade 2-4 TIPN was significantly higher in the once weekly paclitaxel versus once every 3 weeks docetaxel arm by both physician-rated CTCAE (45% v 29%; P = .02) and PRO-CTCAE (40% v 24%; P = .03). Patients receiving once weekly paclitaxel required more dose reductions because of TIPN (28% v 9%; P < .001) or any cause (39% v 25%; P = .02)., Conclusion: Germline variation did not predict risk of TIPN in Black women receiving (neo)adjuvant once weekly paclitaxel or once every 3 weeks docetaxel. Once weekly paclitaxel was associated with significantly more grade 2-4 TIPN and required more dose reductions than once every 3 weeks docetaxel.
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- 2024
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17. A Cohort Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms: Results from ECOG-ACRIN E1Z11.
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Stearns V, Jegede OA, Chang VT, Skaar TC, Berenberg JL, Nand R, Shafqat A, Jacobs NL, Luginbuhl W, Gilman P, Benson AB 3rd, Goodman JR, Buchschacher GL Jr, Henry NL, Loprinzi CL, Flynn PJ, Mitchell EP, Fisch MJ, Sparano JA, and Wagner LI
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- Humans, Female, Middle Aged, Aged, Prospective Studies, Anastrozole therapeutic use, Anastrozole adverse effects, Anastrozole administration & dosage, Cohort Studies, Postmenopause, Aged, 80 and over, Patient Reported Outcome Measures, Aromatase genetics, Aromatase Inhibitors therapeutic use, Aromatase Inhibitors adverse effects, Polymorphism, Single Nucleotide, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Breast Neoplasms pathology
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Purpose: Aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) are common and frequently lead to AI discontinuation. SNPs in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate the association between 10 SNPs and AI discontinuation due to AIMSS., Patients and Methods: Postmenopausal women with stage I to III hormone receptor-positive breast cancer received anastrozole 1 mg daily and completed patient-reported outcome measures to assess AIMSS (Stanford Health Assessment Questionnaire) at baseline, 3, 6, 9, and 12 months. We estimated that 40% of participants would develop AIMSS and 25% would discontinue AI treatment within 12 months. Enrollment of 1,000 women with a fixed number per racial stratum provided 80% power to detect an effect size of 1.5 to 4. SNPs were found in ESR1 (rs2234693, rs2347868, and rs9340835), CYP19A1 (rs1062033 and rs4646), TCL1A (rs11849538, rs2369049, rs7158782, and rs7159713), and HTR2A (rs2296972)., Results: Of the 970 evaluable women, 43% developed AIMSS and 12% discontinued AI therapy within 12 months. Although more Black and Asian women developed AIMSS than White women (49% vs. 39%, P = 0.017; 50% vs. 39%, P = 0.004, respectively), the AI discontinuation rates were similar across groups. None of the SNPs were significantly associated with AIMSS or AI discontinuation in the overall population or in distinct cohorts. The OR for rs2296972 (HTR2A) approached significance for developing AIMSS., Conclusions: We were unable to prospectively validate candidate SNPs previously associated with AI discontinuation due to AIMSS. Future analyses will explore additional genetic markers, patient-reported outcome predictors of AIMSS, and differences by race., (©2024 American Association for Cancer Research.)
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- 2024
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18. A Phase I/II Study of GSK525762 Combined with Fulvestrant in Patients with Hormone Receptor-positive/HER2-negative Advanced or Metastatic Breast Cancer.
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Cescon DW, Hilton J, Morales Murilo S, Layman RM, Pluard T, Yeo B, Park IH, Provencher L, Kim SB, Im YH, Wyce A, Krishnatry AS, Hicks K, Zhang Q, Barbash O, Khaled A, Horner T, Dhar A, Oliveira M, and Sparano JA
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- Humans, Female, Fulvestrant, Nuclear Proteins, Receptor, ErbB-2 metabolism, Transcription Factors, Disease Progression, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bromodomain Containing Proteins, Cell Cycle Proteins, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Breast Neoplasms pathology, Benzodiazepines
- Abstract
Purpose: Endocrine-based therapy is the initial primary treatment option for hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC). However, patients eventually experience disease progression due to resistance to endocrine therapy. Molibresib (GSK525762) is a small-molecule inhibitor of bromodomain and extraterminal (BET) family proteins (BRD2, BRD3, BRD4, and BRDT). Preclinical data suggested that the combination of molibresib with endocrine therapy might overcome endocrine resistance. This study aimed to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy [objective response rate (ORR)] of molibresib combined with fulvestrant in women with HR+/HER2- mBC., Patients and Methods: In this phase I/II dose-escalation and dose-expansion study, patients received oral molibresib 60 or 80 mg once daily in combination with intramuscular fulvestrant. Patients enrolled had relapsed/refractory, advanced/metastatic HR+/HER2- breast cancer with disease progression on prior treatment with an aromatase inhibitor, with or without a cyclin-dependent kinase 4/6 inhibitor., Results: The study included 123 patients. The most common treatment-related adverse events (AE) were nausea (52%), dysgeusia (49%), and fatigue (45%). At a 60-mg dosage of molibresib, >90% of patients experienced treatment-related AE. Grade 3 or 4 treatment-related AE were observed in 47% and 48% of patients treated with molibresib 60 mg and molibresib 80 mg, respectively. The ORR was 13% [95% confidence interval (CI), 8-20], not meeting the 25% threshold for proceeding to phase II. Among 82 patients with detected circulating tumor DNA and clinical outcome at study enrollment, a strong association was observed between the detection of copy-number amplification and poor progression-free survival (HR, 2.89; 95% CI, 1.73-4.83; P < 0.0001)., Conclusions: Molibresib in combination with fulvestrant did not demonstrate clinically meaningful activity in this study., (©2023 The Authors; Published by the American Association for Cancer Research.)
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- 2024
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19. U.S. payer budget impact of using an AI-augmented cancer risk discrimination digital histopathology platform to identify high-risk of recurrence in women with early-stage invasive breast cancer.
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Masud SF, Mark N, Goss T, Malinowski D, Schnitt SJ, Sparano JA, and Donovan MJ
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- Humans, Female, Risk Assessment, Decision Trees, Chemotherapy, Adjuvant economics, Cost-Benefit Analysis, United States, Artificial Intelligence, Neoplasm Staging, Middle Aged, Breast Neoplasms pathology, Neoplasm Recurrence, Local, Markov Chains
- Abstract
Aims: Use of gene expression signatures to predict adjuvant chemotherapy benefit in women with early-stage breast cancer is increasing. However, high cost, limited access, and eligibility for these tests results in the adoption of less precise assessment approaches. This study evaluates the cost impact of PreciseDx Breast (PDxBr), an AI-augmented histopathology platform that assesses the 6-year risk of recurrence in early-stage invasive breast cancer patients to help improve informed use of adjuvant chemotherapy., Materials and Methods: A decision-tree Markov model was developed to compare the costs of treatment guided by standard of care (SOC) risk assessment (i.e. clinical diagnostic workup with or without Oncotype DX) versus PDxBr with SOC in a hypothetical cohort of U.S. women with early-stage invasive breast cancer. A commercial payer perspective compares costs of testing, adjuvant therapy, recurrence, adverse events, surveillance, and end-of-life care., Results: PDxBr use in prognostic evaluation resulted in savings of $4 million (M) in year one compared to current SOC in 1 M females members. Over 6-years, savings increased to $12.5 M. The per-treated patient costs in year one amounted to $19.5 thousand (K) for SOC and $16.9K for PDxBr., Limitations: For simplicity, recurrence was not specified. We performed scenario analyses to account for variations in rates for local, regional, and distant recurrence. Second, a recurrent patient incurs the total cost of treated recurrence in the first year and goes back to remission or death. Third, CDK4/6i treatment is only incorporated in the recurrence costs but not in the first line of treatment for early-stage breast cancer due to limited data., Conclusions: Sensitivity analyses demonstrated robust overall savings to changes in all variables in the model. The use of PDxBr to assess breast cancer recurrence risk has the potential to fill gaps in care and reduce costs when gene expression signatures are not available.
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- 2024
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