We found a consistent pattern of better QOL outcomes at each follow-up assessment during the first 6 months of treatment for orchiectomized patients with metastatic prostate cancer who received placebo versus flutamide. Improvement over time was evident in both treatment groups but more so for patients receiving placebo.

Background Multi-gene tumor assays have provided clinically useful prognostic information for pts with HR receptor and node-positive breast cancer. The 21-gene RS was shown to be prognostic for pts treated with tamoxifen alone, and exploratory studies suggested that it may be predictive of benefit from chemotherapy. In retrospective analyses from SWOG S8814, pts with low RS appeared to get no benefit from adjuvant CAF chemotherapy, while those with higher RS did. These retrospective data require validation, especially since more modern chemotherapy might be more effective than the regimen used in S8814. Specific Aims/Trial Design: In January 2011, SWOG activated a phase III randomized clinical trial (registration number NCT01272037) to test the efficacy of using modern chemotherapy regimens in node positive pts with low RS, whose prognosis is still moderately poor but may not benefit from adjuvant chemotherapy based on tumor biology predicted by the RS value. The trial is similar to the Tailor RX study, but focuses on a node-positive population with low and intermediate RS. Eligibility Criteria: Pts with 1 to 3 positive lymph nodes, HR-positive and HER2−negative invasive breast cancer with RS ≤ 25 are eligible for randomization. Pts will be informed of their RS. Target and Present Accrual: Approximately 9400 patients will be screened to randomize 4000, stratified by RS (0-13 vs. 14–25), menopausal status, and axillary surgery (sentinel node vs. complete dissection); 46 are presently registered. Statistical Methods: The trial is powered to find a significant interaction of treatment assignment and the continuous RS value and, subsequently, derive a cut point for using the assay to guide treatment decisions. Pts who consent to screening are required to consent to banking of the tumor tissue and blood for further studies. Patient Reported Outcomes will be collected pre, post-screening and post-randomization. The study also has a cost-effectiveness analysis. Funding: Supported in part by National Cancer Institute grants CA32102 & CA38926, and in part by the Susan G. Komen for the Cure® Research Program, and the Breast Cancer Research Foundation. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-03-01.

Background: Adherence to AI therapy for adjuvant treatment of hormone receptor-positive breast cancer is poor, primarily because of AIMSS. Premature discontinuation of AI therapy can lead to increased likelihood of breast cancer recurrence. Duloxetine (dulox) is a serotonin norepinephrine reuptake inhibitor that is FDA-approved for treatment of multiple chronic pain disorders. Phase II data from an open label trial of dulox for treatment of AIMSS demonstrated a 61% improvement in pain. We hypothesized that treatment of AIMSS with dulox would improve average joint pain compared to placebo (plac). Methods: Postmenopausal women with stage I-III breast cancer who had been taking AI therapy for between 3 wks and 36 mo were enrolled. To be eligible, patients were required to have average pain of ≥4/10 using the Brief Pain Inventory (BPI) that developed or worsened since AI therapy initiation, and not have any contraindications to dulox therapy. Patients were randomized 1:1 to dulox 30 mg daily for 7 d then 60 mg daily for 11 wks then 30 mg daily for 7 d, or to matching plac, stratified by baseline pain (4-6 vs 7-10) and prior taxane use (yes vs no). Pain, depression, and quality of life (QoL) were assessed after 2, 6, and 12 wks of therapy, as well as at the 24 wk time point. The primary analysis used linear mixed models to examine average pain through 12 wks by arm, adjusting for the stratification factors and assessment time. Clinically significant change in average pain was defined as a ≥2-point decrease from baseline. Results: 299 patients were randomized between June 2013 and October 2015, 10 of whom were ineligible. 127 dulox-treated and 128 plac-treated patients were evaluable for the primary analysis. No sizeable imbalances in baseline factors were noted by arm. Seventeen pts reported grade 3 adverse events (AEs) (dulox: 12/138 (8.7%), plac: 5/141 (3.5%)), and 40 pts discontinued treatment because of AEs (dulox: 21 (52.5%), plac: 19 (47.5%)). Mean observed average pain, the proportion of pts experiencing clinically significant change in average pain from baseline, and percent reduction in average pain all indicated greater improvement for dulox compared with plac through 12 wks, but were similar by arm at wk 24 (12 wks after completion of intervention; see Table). In multivariable linear mixed model analysis, the BPI average pain was reduced on average by 0.82 points more on dulox compared to plac over the first 12 wks (95% CI -1.24 to -0.40, p=0.0002). Similar patterns were observed for worst pain, pain interference, joint pain, stiffness, and functioning, and QoL. Table: Observed Average Pain Scores by Assessment TimeTime PointBaseline2 weeks6 weeks12 weeks24 weeksduloxplacduloxplacduloxplacduloxplacduloxplacAverage pain5.445.493.514.412.953.962.913.453.373.42Percent reduction--34%20%46%28%46%36%37%37%Patients with clinically significant change--54%44%69%49%69%60%60%59% Conclusions: Treatment with duloxetine was superior to placebo for the treatment of AIMSS among women with early stage breast cancer, was well tolerated, and was associated with improvements in QoL. Clinicaltrials.gov NCT01598298. Citation Format: Henry NL, Unger JM, Schott AF, Fehrenbacher L, Flynn PJ, Prow D, Sharer CW, Lew DL, Moseley A, Fisch MJ, Moinpour C, Hershman DL, Wade III JL. Randomized, placebo-controlled trial of duloxetine for aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) in early stage breast cancer (SWOG S1202) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S5-06.