Citations 2
A single-arm, phase II study of sequential therapy with curative intent in de novo HER2+ metastatic breast cancer: The SAPPHO study.
Ruddy, Kathryn Jean, Heiling, Hillary, Rozenblit, Mariya, Dees, Elizabeth Claire , Frey, Anna , Ossing, Sarah, Koegel, Susan, LaScala, Jamie, Brown, Thelma, Tolaney, S M, Carey, L, Krop, Ian E., Tayob, Nabihah, Winer, Eric P., Rimawi, Mothaffar, Parsons, Heather A. , Lin, Nancy U., Morganti, Stefania , Ruddy, Kathryn J. , Heiling, Hillary , Rozenblit, Mariya , Stoeckle, James Hart , Pradhan, Deepti , Carey, Lisa A. , Krop, Ian E. , Tayob, Nabihah , Winer, Eric P. , Rimawi, Mothaffar, Lin, Nancy U.
Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: No page available
10.1200/jco.2026.44.16_suppl.tps1147
TPS1147 Background: Due to dramatic improvements in neoadjuvant and adjuvant HER2-directed therapy (tx), most patients (pts) with early HER2+ breast cancer are cured. As a result, over half of pts newly diagnosed with HER2+ metastatic breast cancer (MBC) now present with de novo stage IV disease. Anti-HER2 tx has also significantly extended survival for pts with HER2+ MBC, with a subgroup of exceptional responders alive many years (yrs) after diagnosis. However, the paradigm for HER2+ MBC remains non-curative, and pts receive tx indefinitely with significant toxicities and costs. The SAPPHO study is investigating whether an intensification approach of sequential, non-cross resistant anti-HER2 tx followed by tx discontinuation is associated with long-term disease control in pts with HER2+ MBC. Methods: SAPPHO is an open-label, phase II, single-arm trial testing a sequential regimen of non-cross resistant, HER2-targeted tx with curative intent in pts with de novo HER2+ MBC. Eligible pts must have biopsy-proven, de novo MBC with high HER2 expression (3+ by immunohistochemistry). Pts with brain metastases are eligible upon receipt of local tx. Treatment consists of an induction regimen (trastuzumab-pertuzumab-taxane [THP] x 4 cycles, followed by trastuzumab deruxtecan [TDXd] x 6 cycles, followed by trastuzumab emtansine [TDM1]-tucatinib x 4 cycles), followed by a maintenance regimen (HP-tucatinib for 1 yr). Given results from DESTINY-Breast09, the sequence of TDXd-P x 6 cycles followed by THP x 4 followed by TDM1-tucatinib x 4 can be chosen as alternative induction tx per investigator and patient choice. Pts who remain progression-free after completing maintenance will stop all anti-HER2 tx. Endocrine tx will be continued for pts with hormone receptor+/HER2+ tumors. Tumor specimens from breast and a metastatic site are collected at baseline and the end of induction. Serial plasma samples for ctDNA analysis are collected at baseline, during treatment, and during follow-up. The primary endpoint is the probability of being progression-free and off anti-HER2 tx 4 yrs from the start of induction. With a sample size of 72 pts, the study is designed to have 91% power to reject the null hypothesis that the probability of being off anti-HER2 tx and progression-free is less than 24%, with an alternative hypothesis of 40%. Key secondary endpoints are overall survival, overall response rate by modified RECIST 1.1 after induction, and safety. Correlative endpoints include the relationship between ctDNA dynamics and outcomes. Patient-reported outcomes will be analyzed, including quality of life, illness intrusiveness, financial toxicity, anxiety, distress about cancer progression, perception of benefit and risk of progression. SAPPHO began enrollment in Q3 2024, and the study is open at 4 US sites within the Translational Breast Cancer Research Consortium (NCT05721248). Clinical trial information: NCT05721248 .
Factors Associated With Large Improvements in Health-Related Quality of Life in Patients With Atrial Fibrillation
Holmes, DaJuanicia N. , Pieper, Karen S. , Ezekowitz, Michael D. , Fonarow, Gregg C. , Gersh, Bernard J. , Kowey, Peter R. , Mahaffey, Kenneth W. , Reiffel, James A. , Singer, Daniel E. , Piccini, Jonathan P. , Mendelson, R. A., NEUTEL, J, Pan, Dengji, Poock, James J., Raffetto, J.D., Greengold, R., Roan, P G, Saba, F., Sackett, Melanie K., Schneider, R., Seymour, Zachary , Shanes, Jeffrey G., Smiley, Nasser, Smith, David H. , Snipes, C., Sotolongo, Rodolfo, Staniloae, Cezar , Stoltz, S., Suresh, D.P. , Tak, Tahir , Tannenbaum, A., Turk, Samir, Vora, Kishor, Randhawa, P., Zebrack, James S., Silva, Eduardo , Riley, Edward T., Weinstein, D., Vasiliauskas, Tomas, Goldbarg, Seth , Yarlagadda, Chakri, Laurion, D., Osunkoya, A., Burns, Richéal , Castor, Tatsiana , Luttman, C., Anton, Stephen D. , McGarvey, Jeremy R., Guthrie, Robert D., Deriso, George T., Flood, Raymond, Fleischer, L H, Fierstein, J.S., Jacobs, George B., Adjei, Nasser, Akyea-Djamson, Ayim, Bacon, Jenny , Bedwell, Noel W., Berger, PB, Berry, Joni I., Bhagwat, Ravi, Boccalandro, Fernando , Capó, Jaïr Dilmé, Kapadia, Sumit, Casanova, Rene, Morriss, J.E., Elsen, J., Farsad, Ramin, Fox, David J. , Frandsen, Brad, Gelernt, M., Hall, Cassandra L. , Hotchkiss, David R. , Ip, J., Jaffrani, Naseem, Kazmierski, John F., Waxman, F., Kneller, G. Larsen, Labroo, Ajay, Jaffe, Bernard M., Lebenthal, Mark, Lillestol, Michael, Leclerc, Kenneth M. , Maccaro, Paul, Mayer, Nolan, Kozłowski, J , Benjamin, Sanford P., Detweiler, Robert, Igic, Petar, Jackson, Tatum, Pappas, Janine, Littlefield, Ryan , Frey, Anna , Vranian, Robert B., Long, W., Grena, Paul, Arouni, Amy , Quinn, John , Blonder, Ronald, Snyder, H., Slabic, S., Cohen, Kenneth D., Walthall, W. W., Snoddy, Brian, Alvarado, Olga Franco, Leach, Corinne L., Rothman, Steven A., Olatidoye, Abiodun G, Almahameed, Soufian , Rosenthal, Shelly, Reiter, William M., Thompson, T., Thew, Stephen, Kobayashi, Junji , Williams, M., Kramer, Joel H. , Latif, Sidrah , Rhee, B., Ruiz-Serrano, D., Stringam, Stanley, Wolok, K., Focil, Augusto, Butman, Samuel, Ingersoll, Henry, Borge, R. P., Al-Saghir, Y., Farris, Neil, Shore, Karen, Gornick, C., Eilat, P., Paliwal, Y., Mitra, Rito , Jingo, Ahmad, Aslam, Asma , Watson, Robert, Voyce, Stephen , Turakhia, Mintu P. , Goytia-Leos, D., Lurie, Miriam, Mallis, G., Strobel, John, Fisher, D M, Atieh, Mutaz I., Drabick, Andrew, Harman, Ece, Ashcraft, B., Krista, M., Videlefsky, A., Zayas, E. Rivera, Tan, A.E., Gersh, Bernard J , Turakhia, Mintu P , Steinberg, Benjamin A. , Allen, Larry A. , Chan, Paul S. , Freeman, James V. , Hylek, Elaine M. , Naccarelli, Gerald V. , Peterson, Eric D. , Mendelson, R., AL-NAHHAS, ADIL M. , Padanilam, B., Pan, D., Raffetto, J., Roan, P., Sackett, M., Seymour, Z., Shoemaker, J. Kevin , Simms, V., Tak, T., Riley, E., Weinstein, D., Hayward, D., Burns, R., Spiller, D., McGarvey, J., Guthrie, R., Flood, R., Aggarwal, R., Jacobs, G., Alfieri, A., Bacon, J., Berger, P., Berry, J., Bloom, S., Kapadia, S., Casanova, R., Christensen, T., Fox, D., Gill, S., Grubb, Søren , Hall, C., Harris, H., Hotchkiss, D., Jones, A., Lee, David S. , Kozlowski, J., Benjamin, S., Detweiler, R., Jackson, T., Littlefield, R., Long, W., Quinn, J., Browne, Kevin D. , Forman, Steven L. , Ebinger, Martin , Williams, David Michael , Stein, R., Kirkland, S., Cohen, K., Walthall, W., Davis, Keith L. , Alvarado, O., Leach, C., Sharma, Anand , Sutter, G., Reiter, W., Kobayashi, J., Kramer, J., Latif, S.A., Adler, Alma J , Butman, Samuel M. , Coats, Paul , Shore, K., Schwartz, M.B., Quinlan, E., Mitra, R., Aslam, A.A., Lurie, M., Atwater, Brett D. , Murray, John M. , Fisher, D., Landes, Reid D. , Harman, E., Zayas, E. Rivera
Circulation: Arrhythmia and Electrophysiology | April 16, 2020 | Volume: 13 | Issue: 5 | Pages: No page available
Background: Atrial fibrillation (AF) adversely impacts health-related quality of life (hrQoL). While some patients demonstrate improvements in hrQoL, the factors associated with large improvements in hrQoL are not well described. Methods: We assessed factors associated with a 1-year increase in the Atrial Fibrillation Effect on Quality-of-Life score of 1 SD (≥18 points; 3× clinically important difference), among outpatients in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation I registry. Results: Overall, 28% (181/636) of patients had such a hrQoL improvement. Compared with patients not showing large hrQoL improvement, they were of similar age (median 73 versus 74, P =0.3), equally likely to be female (44% versus 48%, P =0.3), but more likely to have newly diagnosed AF at baseline (18% versus 8%; P =0.0004), prior antiarrhythmic drug use (52% versus 40%, P =0.005), baseline antiarrhythmic drug use (34.8% versus 26.8%, P =0.045), and more likely to undergo AF-related procedures during follow-up (AF ablation: 6.6% versus 2.0%, P =0.003; cardioversion: 12.2% versus 5.9%, P =0.008). In multivariable analysis, a history of alcohol abuse (adjusted OR, 2.41; P =0.01) and increased baseline diastolic blood pressure (adjusted OR, 1.23 per 10-point increase and >65 mm Hg; P =0.04) were associated with large improvements in hrQoL at 1 year, whereas patients with prior stroke/transient ischemic attack, chronic obstructive pulmonary disease, and peripheral arterial disease were less likely to improve ( P <0.05 for each). Conclusions: In this national registry of patients with AF, potentially treatable AF risk factors are associated with large hrQoL improvement, whereas less reversible conditions appeared negatively associated with hrQoL improvement. Understanding which patients are most likely to have large hrQoL improvement may facilitate targeting interventions for high-value care that optimizes patient-reported outcomes in AF. Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01165710.