Melody A Cobleigh1,2, Stewart J Anderson1,3, Kalliopi P Siziopikou1,4, Douglas W Arthur1,5, Rachel Rabinovitch1,6, Thomas B Julian1,7, David S Parda1,7, Samantha A Seaward1,8, Dennis L Carter9,10, Janice A Lyons11, Melissa S Dillmon12, Gustav C Magrinat1,13, Vivek S Kavadi1,10, Allison M Zibelli14, Lavanya Tiriveedhi1,15, Matthew L Hill1,16, Marianne K Melnik1,17, Sushil Beriwal1,18, Eleftherios P Mamounas1,19, Norman Wolmark1,3. 1. NRG Oncology, Pittsburgh, PA. 2. Rush University Medical Center, Chicago, IL. 3. University of Pittsburgh, Pittsburgh, PA. 4. Northwestern University Feinberg School of Medicine, Chicago, IL. 5. Massey Cancer Center, Virginia Commonwealth University, Richmond, VA. 6. University of Colorado Cancer Center, Aurora, CO. 7. Allegheny Health Network, Pittsburgh, PA. 8. Kaiser Permanente Cancer Research Program, Vallejo, CA. 9. Rocky Mountain Cancer Centers, Aurora, CO. 10. US Oncology, The Woodlands, TX. 11. University Hospitals Seidman Cancer Center, Cleveland, OH. 12. Harbin Clinic, Rome, GA. 13. Cone Health Center, Greensboro, NC. 14. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA. 15. Mercy Clinic Cancer and Hematology, Springfield, MO. 16. Mission Cancer and Blood, Des Moines, IA. 17. Cancer Research Consortium of West Michigan, Grand Rapids, MI. 18. UPMC Hillman Cancer Center, Magee Womens Hospital, Pittsburgh, PA. 19. Orlando Health UF Health Cancer Center, Orlando, FL.
Abstract
PURPOSE: Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS). PATIENTS AND METHODS: Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years. RESULTS: There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years. CONCLUSION: Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy.
PURPOSE: Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS). PATIENTS AND METHODS: Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years. RESULTS: There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years. CONCLUSION: Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy.
Authors: Syed K Mohsin; Heidi L Weiss; M Carolina Gutierrez; Gary C Chamness; Rachel Schiff; Michael P Digiovanna; Chun-Xia Wang; Susan G Hilsenbeck; C Kent Osborne; D Craig Allred; Richard Elledge; Jenny C Chang Journal: J Clin Oncol Date: 2005-02-14 Impact factor: 44.544
Authors: Lindy L Visser; Lotte E Elshof; Michael Schaapveld; Koen van de Vijver; Emma J Groen; Mathilde M Almekinders; Carolien Bierman; Flora E van Leeuwen; Emiel J Rutgers; Marjanka K Schmidt; Esther H Lips; Jelle Wesseling Journal: Clin Cancer Res Date: 2018-04-23 Impact factor: 12.531
Authors: Irene L Wapnir; James J Dignam; Bernard Fisher; Eleftherios P Mamounas; Stewart J Anderson; Thomas B Julian; Stephanie R Land; Richard G Margolese; Sandra M Swain; Joseph P Costantino; Norman Wolmark Journal: J Natl Cancer Inst Date: 2011-03-11 Impact factor: 13.506
Authors: Jack Cuzick; Ivana Sestak; Sarah E Pinder; Ian O Ellis; Sharon Forsyth; Nigel J Bundred; John F Forbes; Hugh Bishop; Ian S Fentiman; William D George Journal: Lancet Oncol Date: 2010-12-07 Impact factor: 41.316