Comparison of Radiation With or Without Concurrent Trastuzumab for HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy: A Phase III Clinical Trial
Melody A Cobleigh, Stewart J Anderson, Kalliopi P Siziopikou, Douglas W Arthur, Rachel Rabinovitch, Thomas B Julian, David S Parda, Samantha A Seaward, Dennis L Carter, Janice A Lyons, Melissa S Dillmon, Gustav C Magrinat, Vivek S Kavadi, Allison M Zibelli, Lavanya Tiriveedhi, Matthew L Hill, Marianne K Melnik, Sushil Beriwal, Eleftherios P Mamounas, Norman Wolmark, Melody A Cobleigh, Stewart J Anderson, Kalliopi P Siziopikou, Douglas W Arthur, Rachel Rabinovitch, Thomas B Julian, David S Parda, Samantha A Seaward, Dennis L Carter, Janice A Lyons, Melissa S Dillmon, Gustav C Magrinat, Vivek S Kavadi, Allison M Zibelli, Lavanya Tiriveedhi, Matthew L Hill, Marianne K Melnik, Sushil Beriwal, Eleftherios P Mamounas, Norman Wolmark
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.
Trial registration: ClinicalTrials.gov NCT00769379.
Conflict of interest statement
Melody A. CobleighConsulting or Advisory Role: Roche/Genentech, Immunomedics, Genomic Health, Puma Biotechnology, Seattle GeneticsResearch Funding: Macrogenics, Radius Health, Genentech/Roche, Seattle Genetics, Zymeworks, SynthonPatents, Royalties, Other Intellectual Property: Genomic HealthTravel, Accommodations, Expenses: Genentech, Immunomedics, Puma Biotechnology, Seattle Genetics Stewart J. AndersonConsulting or Advisory Role: Jazz Pharmaceuticals Kalliopi P. SiziopikouHonoraria: Ventana Medical Systems, Lilly, Merck Douglas W. ArthurStock and Other Ownership Interests: Advanced Radiation Therapy Rachel RabinovitchStock and Other Ownership Interests: Abbott Laboratories, Bristol-Myers Squibb, Intuitive Surgical, IDEXX LaboratoriesResearch Funding: Prelude Therapeutics Dennis L. CarterEmployment: Rocky Mountain Cancer Centers Melissa S. DillmonStock and Other Ownership Interests: Johnson & JohnsonConsulting or Advisory Role: Puma Biotechnology Vivek S. KavadiEmployment: US Oncology Network Matthew L. HillStock and Other Ownership Interests: AstraZeneca, Newlink Genetics, Kazia Therapeutics, Leap Therapeutics, OncoSec, MEI Pharma, PLx Pharma, Radius Health, Crispr Therapeutics, Cassava Sciences Sushil BeriwalHonoraria: Varian Medical Systems, XOFT Eleftherios P. MamounaHonoraria: Genentech/Roche, Genomic Health, PreciscaConsulting or Advisory Role: Genomic Health, BioTheranostics, Roche/Genentech, Merck, Daiichi Sankyo, Puma Biotechnology, PreciscaSpeakers' Bureau: Genomic Health, Genentech/RocheTravel, Accommodations, Expenses: Genomic Health, Genentech/RocheNo other potential conflicts of interest were reported.
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Source: PubMed