Randomized Controlled Phase II Evaluation of Two Dose Levels of Bupropion Versus Placebo for Sexual Desire in Female Cancer Survivors: NRG-CC004.

PURPOSE: Because of the negative impact of cancer treatment on female sexual function, effective treatments are warranted. The purpose of this multisite study was to evaluate the ability of two dose levels of extended-release bupropion, a dopaminergic agent, to improve sexual desire more than placebo at 9 weeks, measured by the desire subscale of the Female Sexual Function Index (FSFI), and to evaluate associated toxicities. METHODS: Postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (< 3.3), who had completed definitive cancer therapy, were eligible. Women were randomly assigned to receive 150 mg or 300 mg once daily of extended-release bupropion or a matching placebo. t-tests were performed on the FSFI desire subscale to evaluate whether there was a significantly greater change from baseline to 9 weeks between placebo and each bupropion arm as the primary end point. Sixty-two patients per arm provided 80% power using a one-sided t-test. RESULTS: Two hundred thirty women were randomly assigned from 72 institutions through the NRG Oncology NCORP network. At 9 weeks, there were no statistically significant differences in change of the desire subscale scores between groups; participants in all three arms reported improvement. The mean changes for each arm were placebo 0.62 (standard deviation [SD] = 1.18), 150-mg once daily bupropion 0.64 (SD = 0.95), and 300-mg once daily bupropion 0.60 (SD = 0.89). Total and subscale scores on the FSFI were low throughout the study, indicating dysfunction in all groups. CONCLUSION: Bupropion was not more effective than placebo in improving the desire subscale of the FSFI. Subscale and total scores of the FSFI demonstrated dysfunction throughout the 9 weeks of the study. More research is needed to support sexual function in female cancer survivors.

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.