Comparison of Radiation With or Without Concurrent Trastuzumab for HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy: A Phase III Clinical Trial.

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.

Adjuvant vaginal cuff brachytherapy for high-risk, early stage endometrial cancer.

PURPOSE: To report outcomes following adjuvant high-dose-rate vaginal brachytherapy (VBT) with or without chemotherapy for high-intermediate risk (HIR) and high-risk, early stage endometrial cancer as defined in Gynecologic Oncology Group trial 0249. MATERIAL AND METHODS: From May 2000 to January 2014, 68 women with HIR and high-risk endometrial cancer underwent surgical staging followed by VBT. Median VBT dose was 21 Gy delivered in three fractions prescribed to 0.5 cm depth. Paclitaxel 175 mg/m(2) and carboplatin area under the curve 6 was administered every 21 days in sequence with VBT. Actuarial survival estimates were calculated using the Kaplan-Meier method. RESULTS: Patient demographics included a median age of 66 years (range: 36-91) and stages IA (49%), IB (38%), and II (13%), respectively. Thirty-one (46%) patients had HIR disease with endometrioid histology, and 33 (48%) patients had serous or clear cell histology. Thirty-seven (54%) patients received a median 3 cycles (range: 3-6) of chemotherapy in addition to VBT, and 65 patients (96%) completed all prescribed therapy. During a median follow up of 33.1 months (range: 4.0-161.7), four patients have recurred, including one vaginal recurrence. The 3-year estimates of vaginal, pelvic, and distant recurrences were 1.9%, 2.4%, and 9.1%, respectively. The 3-year rates of disease-free and overall survival were 87.7% and 93.9%, respectively. CONCLUSIONS: Early outcomes with adjuvant VBT with or without chemotherapy demonstrate high rates of vaginal and pelvic control for women with HIR disease. Early vaginal and pelvic relapses in high-risk patients suggest that pelvic external beam radiotherapy is warranted in this subgroup, but additional data from large phase III trials is warranted.