Methods to Standardize a Multicenter Acupuncture Trial Protocol to Reduce Aromatase Inhibitor-related Joint Symptoms in Breast Cancer Patients

AbstractRobust methods are needed to efficiently conduct large, multisite, randomized, controlled clinical trials of acupuncture protocols. The Southwest Oncology Group (SWOG) S1200 trial is a randomized, controlled (i.e., sham-controlled and waitlist-controlled) trial of a standardized acupuncture protocol for treating aromatase inhibitor (AI)-associated arthralgias in early-stage breast cancer patients (n = 228). The primary objective of this study was to determine whether true acupuncture administered twice weekly for 6 weeks, as compared to sham acupuncture or a waitlist control, reduced AI-associated joint pain at 6 weeks as assessed by patient reports. The study was conducted at 11 institutions across the United States. The true acupuncture protocol was developed using a consensus-based process. The true acupuncture and the sham acupuncture protocols each consisted of 12 sessions administered for 6 weeks, followed by one weekly session for 6 weeks. The true acupuncture protocol used standardized protocol points, and the standardized acupoints were tailored to a patient's joint symptoms. The similarly standardized sham acupuncture protocol utilized superficial needling of nonacupoints. Standardized methods were developed to train and monitor acupuncturists and included online and in-person training, study manuals, monthly phone calls, and remote quality assurance monitoring throughout the study period. The research staff similarly received online and in-person training and monthly phone calls

Association between body mass index and response to duloxetine for aromatase inhibitor‐associated musculoskeletal symptoms in SWOG S1202

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149517/1/cncr32024.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149517/2/cncr32024_am.pd

Phase II Trial of Simple Oral Therapy with Capecitabine and Cyclophosphamide in Patients with Metastatic Breast Cancer: SWOG S0430

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139899/1/onco0179.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139899/2/onco0179-sup-0001.pd

Overall Survival with Fulvestrant plus Anastrozole in Metastatic Breast Cancer

BACKGROUND We previously reported prolonged progression-free survival and marginally prolonged overall survival among postmenopausal patients with hormone receptor-positive metastatic breast cancer who had been randomly assigned to receive the aromatase inhibitor anastrozole plus the selective estrogen-receptor down-regulator fulvestrant, as compared with anastrozole alone, as first-line therapy. We now report final survival outcomes. METHODS We randomly assigned patients to receive either anastrozole or fulvestrant plus anastrozole. Randomization was stratified according to adjuvant tamoxifen use. Analysis of survival was performed by means of two-sided stratified log-rank tests and Cox regression. Efficacy and safety were compared between the two groups, both overall and in subgroups. RESULTS Of 707 patients who had undergone randomization, 694 had data available for analysis. The combination-therapy group had 247 deaths among 349 women (71%) and a median overall survival of 49.8 months, as compared with 261 deaths among 345 women (76%) and a median overall survival of 42.0 months in the anastrozole-alone group, a significant difference (hazard ratio for death, 0.82; 95% confidence interval (CIS, 0.69 to 0.98; P=0.03 by the log-rank test). In a subgroup analysis of the two strata, overall survival among women who had not received tamoxifen previously was longer with the combination therapy than with anastrozole alone (median, 52.2 months and 40.3 months, respectively; hazard ratio, 0.73; 95% CI, 0.58 to 0.92); among women who had received tamoxifen previously, overall survival was similar in the two groups (median, 48.2 months and 43.5 months, respectively; hazard ratio, 0.97; 95% CI, 0.74 to 1.27) (P=0.09 for interaction). The incidence of long-term toxic effects of grade 3 to 5 was similar in the two groups. Approximately 45% of the patients in the anastrozole-alone group crossed over to receive fulvestrant. CONCLUSIONS The addition of fulvestrant to anastrozole was associated with increased long-term survival as compared with anastrozole alone, despite substantial crossover to fulvestrant after progression during therapy with anastrozole alone. The results suggest that the benefit was particularly notable in patients without previous exposure to adjuvant endocrine therapy.National Cancer Institute; AstraZeneca6 month embargo; published 28 March 2019.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Fulvestrant alone versus fulvestrant and everolimus versus fulvestrant, everolimus and anastrozole: A Phase III randomized, placebo-controlled trial in postmenopausal patients with hormone-receptor-positive stage IV breast cancer: SWOG-Clinical Trials Ini

BACKGROUND: The median survival for women with hormone-receptor-positive (HR+) stage IV metastatic breast cancer (MBC) is 36 months. Strategies to improve outcome for postmenopausal women, include combinations of aromatase inhibitors (AIs) with either the estrogen receptor downregulator fulvestrant, or with the PI3kinase/AKT/mTOR signal inhibitor everolimus, as this pathway has been implicated as a mediator of resistance to endocrine therapies. However,fulvestrant 500 mg has not been tested in combination with everolimus alone, or in combination with everolimus and an AI.SPECIFIC AIMS/TRIAL DESIGN: S1222 (NCT02137837) is a randomized phase III double-blinded, placebo-controlled clinical trial and is currently accruing. Patients receive fulvestrant (500 mg IM every 2 weeks for 3 doses, then monthly) on all arms, everolimus 10 PO daily (Arms 2 and 3, placebo Arm 1), and anastrozole 1 mg daily (Arm 3), or placebo (Arms 2 and 1). The co-primary objectives are to compare progression-free survival (PFS) between fulvestrant and everolimus (Arm 2) vs. fulvestrant (Arm 1), and fulvestrant, everolimus, and anastrozole (Arm 3) vs. fulvestrant (Arm 1). Additional objectives include comparison of PFS between Arms 2 and 3, and overall survival (OS), response and clinical benefit rates, toxicities, feasibility, compliance, and OS among the study arms.Translational research goals are to test molecular determinants of response in circulating tumor cells (CTCs), assess a previously piloted CTC-Endocrine Therapy Index (CTC ETI), perform CTC-Next Generation Sequencing Analysis (CTC-NGS), and NGS on cancer tissue and germ line DNA.ELIGIBILITY CRITERIA: Postmenopausal women with histologically confirmed de novo or newly relapsed stage IV MBC, with HER2-negative and HR-positive (>1% positive nuclear staining) features, with either measurable, or evaluable disease are eligible. Previous neoadjuvant/adjuvant therapy allowed, but adjuvant anti-HR therapy must have been completed ≥ 12 months prior to enrollment.STATISTICAL METHODS/TARGET ACCRUAL: This is a parallel randomized design with equal allocation to the three arms: (1) fulvestrant + placebo for everolimus + placebo for anastrozole; (2) fulvestrant + everolimus + placebo for anastrozole; (3) fulvestrant, everolimus, and anastrozole. PFS is the primary outcome. There are two coprimary hypotheses: (1) Arm 2 versus Arm 1; and (2) Arm 3 versus Arm 1, each will be tested at α = 0.025 (2-sided) .Arm 2 versus Arm 3 is a secondary comparison. Sample size computations are based on accrual of 33 patients per month for 24 months resulting in a computed accrual total of 792. We estimate that the final analysis will occur 24 months after the last patient is accrued, an average followup of 36 months at the time of the final analysis with an expected trial duration of 4 years.*SWOG-CTI manages the non-federally funded components of SWOG under The Hope Foundation. The study is supported by AstraZeneca and Novartis Pharmaceuticals Corp.Citation Format: George Somlo, William Barlow, Halle Moore, Julie Gralow, Anne Schott, Daniel Hayes, Peter Kuhn, James Hicks, Danika Lew, Debu Tripathy, Gabriel Hortobagyl. Fulvestrant alone versus fulvestrant and everolimus versus fulvestrant, everolimus and anastrozole: A Phase III randomized, placebo-controlled trial in postmenopausal patients with hormone-receptor-positive stage IV breast cancer: SWOG-Clinical Trials Ini [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT2-1-01