NSABP B-43

  • Background:
    • A significant amount of ductal carcinoma in situ (DCIS):
      • Is ER-negative and / or overexpresses HER2
    • DCIS is more likely to overexpress HER2:
      • Than invasive cancer, and it is possible that trastuzumab (T) is more likely to be effective in DCIS:
        • Because it intervenes earlier in the carcinogenic pathway
    • HER2 overexpression:
      • Occurs in 45% of estrogen receptor-negative DCIS
      • 20% of ER-positive DCIS
    • Preclinical data suggest that trastuzumab (T):
      • Enhances the effect of radiation in DCIS that overexpresses HER2
    • Based on these findings:
      • The NSABP protocol B-43 aims to evaluate:
        • The effect of trastuzumab in HER2-positive DCIS
      • Patients with HER2-positive DCIS treated with breast-conserving surgery were randomized to breast irradiation versus breast irradiation plus two doses of trastuzumab:
        • Starting on day one of breast irradiation and repeated three weeks later
      • The primary endpoint:
        • Is the development of any breast cancer
  • Methods:
    • After lumpectomy (Lx) for pure DCIS:
      • Each patients (pts) DCIS lesion:
        • Is centrally tested for HER2 using ASCO / CAP guidelines
    • HER2+ pts are randomly assigned to:
      • Receive two doses of T:
        • Three weeks apart during whole breast radiation (WBI) or to WBI alone
  • Eligibility:
    • Women ≥ 18 yrs
    • Margin-clear Lx for pure DCIS
    • ECOG status 0 / 1
    • Clinically or pathologically node negative
  • ER and/or PR status must be known before random assignment
  • Primary aims are to determine:
    • If T decreases:
      • Ipsilateral breast cancer (IBC) recurrence
      • Ipsilateral skin cancer recurrence, or
      • Ipsilateral DCIS
  • Secondary aims are to determine:
    • The benefit of T in:
      • Preventing regional or distant recurrence
      • Contralateral invasive breast cancer or DCIS
  • B-43 will determine if:
    • DFS, recurrence-free interval, and / or overall survival:
      • Can be improved with the use of T
  • 2000 pts will be accrued over 7.9 yrs:
    • With a definitive analysis of primary endpoints performed at 163 IBC events:
      • 7.5 – 8 yrs after protocol initiation with an 80% power to detect a hazard reduction of 36%:
        • From 1.73 IBC events per 100 pt-yrs to 1.11 events per 100 pt-yrs
  • The 36% observed reduction in the hazard of IIBCR-SCR-DCIS on the T arm is based on a projection of 40% hazard reduction if the compliance were perfect, with a 10% noncompliance rate
  • As of January 1, 2013:
  • Results:
    • NSABP B-43 opened 11/9/08
    • As of 7/31/2013:
      • 5,861 patients have had specimens received centrally
      • 5,645 of those had analyzable blocks
      • 1,969 (34.9 %) were HER2 positive
    • A total of 1,428 patients have been accrued:
      • 1,137 (79.6 %) of whom have follow-up information
    • The average follow-up time for the 1,137 patients:
      • Is 23.3 months
    • No grade 4 or 5 toxicity has been observed
    • In NSABP B-43 the HER2-positive rate for pure DCIS among patients undergoing breast-preserving surgery:
      • Is 34.9 %:
        • Lower than the previously reported rate
    • No trastuzumab-related safety signals have been observed
    • Interest in this trial has been robust

#Arrangoiz #BreastSurgeon #BreastCancer #CancerSurgeon #SurgicalOncologist

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