Ingrid A Mayer1, Fengmin Zhao2, Carlos L Arteaga3, William F Symmans4, Ben H Park1, Brian L Burnette5, Amye J Tevaarwerk6, Sofia F Garcia7, Karen L Smith8, Della F Makower9, Margaret Block10, Kimberly A Morley11, Chirag R Jani12, Craig Mescher13, Shabana J Dewani14, Bernard Tawfik15, Lisa E Flaum7, Erica L Mayer16, William M Sikov17, Eve T Rodler18, Lynne I Wagner19, Angela M DeMichele20, Joseph A Sparano9, Antonio C Wolff8, Kathy D Miller21. 1. Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, Nashville, TN. 2. Dana-Farber Cancer Institute, ECOG-ACRIN Biostatistics Center, Boston, MA. 3. UT Southwestern Simmons Cancer Center, Dallas, TX. 4. MD Anderson Cancer Center, Houston, TX. 5. Cancer Research of Wisconsin and Northern Michigan (CROWN) NCORP, Green Bay, WI. 6. University of Wisconsin Carbone Cancer Center, Madison, WI. 7. Northwestern University, Evanston, IL. 8. Johns Hopkins University, Sidney Kimmel Cancer Center, Baltimore, MD. 9. Montefiore Medical Center, Bronx, NY. 10. Alegent Health Bergan Mercy Medical Center, Omaha, NE. 11. Saint Joseph Mercy Hospital, Ann Arbor, MI. 12. Phoebe Putney Memorial Hospital, Albany, GA. 13. Metro-Minnesota Community Oncology Research Consortium, St Louis Park, MN. 14. Columbus Oncology and Hematology Associates Inc, Columbus, OH. 15. University of New Mexico Cancer Center, Albuquerque, NM. 16. Dana-Farber Cancer Institute, Boston, MA. 17. Women and Infants Hospital of Rhode Island, Providence, RI. 18. University of California, Davis, Davis, CA. 19. Wake Forest University Health Sciences, Winston-Salem, NC. 20. University of Pennsylvania/Abramson Cancer Center, Philadelphia, PA. 21. Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN.
Abstract
PURPOSE: Patients with triple-negative breast cancer (TNBC) and residual invasive disease (RD) after completion of neoadjuvant chemotherapy (NAC) have a high-risk for recurrence, which is reduced by adjuvant capecitabine. Preclinical models support the use of platinum agents in the TNBC basal subtype. The EA1131 trial hypothesized that invasive disease-free survival (iDFS) would not be inferior but improved in patients with basal subtype TNBC treated with adjuvant platinum compared with capecitabine. PATIENTS AND METHODS: Patients with clinical stage II or III TNBC with ≥ 1 cm RD in the breast post-NAC were randomly assigned to receive platinum (carboplatin or cisplatin) once every 3 weeks for four cycles or capecitabine 14 out of 21 days every 3 weeks for six cycles. TNBC subtype (basal v nonbasal) was determined by PAM50 in the residual disease. A noninferiority design with superiority alternative was chosen, assuming a 4-year iDFS of 67% with capecitabine. RESULTS: Four hundred ten of planned 775 participants were randomly assigned to platinum or capecitabine between 2015 and 2021. After median follow-up of 20 months and 120 iDFS events (61% of full information) in the 308 (78%) patients with basal subtype TNBC, the 3-year iDFS for platinum was 42% (95% CI, 30 to 53) versus 49% (95% CI, 39 to 59) for capecitabine. Grade 3 and 4 toxicities were more common with platinum agents. The Data and Safety Monitoring Committee recommended stopping the trial as it was unlikely that further follow-up would show noninferiority or superiority of platinum. CONCLUSION: Platinum agents do not improve outcomes in patients with basal subtype TNBC RD post-NAC and are associated with more severe toxicity when compared with capecitabine. Participants had a lower than expected 3-year iDFS regardless of study treatment, highlighting the need for better therapies in this high-risk population.
PURPOSE: Patients with triple-negative breast cancer (TNBC) and residual invasive disease (RD) after completion of neoadjuvant chemotherapy (NAC) have a high-risk for recurrence, which is reduced by adjuvant capecitabine. Preclinical models support the use of platinum agents in the TNBC basal subtype. The EA1131 trial hypothesized that invasive disease-free survival (iDFS) would not be inferior but improved in patients with basal subtype TNBC treated with adjuvant platinum compared with capecitabine. PATIENTS AND METHODS: Patients with clinical stage II or III TNBC with ≥ 1 cm RD in the breast post-NAC were randomly assigned to receive platinum (carboplatin or cisplatin) once every 3 weeks for four cycles or capecitabine 14 out of 21 days every 3 weeks for six cycles. TNBC subtype (basal v nonbasal) was determined by PAM50 in the residual disease. A noninferiority design with superiority alternative was chosen, assuming a 4-year iDFS of 67% with capecitabine. RESULTS: Four hundred ten of planned 775 participants were randomly assigned to platinum or capecitabine between 2015 and 2021. After median follow-up of 20 months and 120 iDFS events (61% of full information) in the 308 (78%) patients with basal subtype TNBC, the 3-year iDFS for platinum was 42% (95% CI, 30 to 53) versus 49% (95% CI, 39 to 59) for capecitabine. Grade 3 and 4 toxicities were more common with platinum agents. The Data and Safety Monitoring Committee recommended stopping the trial as it was unlikely that further follow-up would show noninferiority or superiority of platinum. CONCLUSION: Platinum agents do not improve outcomes in patients with basal subtype TNBC RD post-NAC and are associated with more severe toxicity when compared with capecitabine. Participants had a lower than expected 3-year iDFS regardless of study treatment, highlighting the need for better therapies in this high-risk population.
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