SAN ANTONIO -- Analysis of patient-reported outcomes (PRO), a secondary endpoint of the phase III, NSABP B-35 clinical trial, in which anastrazole and tamoxifen were compared in postmenopausal women with ductal carcinoma in-situ (DCIS) who underwent lumpectomy plus radiotherapy, found that there were no differences in outcomes related to quality of life (QOL) but some differences in outcomes related to symptoms in the two treatment groups, according to data presented at the 2015 San Antonio Breast Cancer Symposium, held Dec. 8-12.
The study confirmed some of the expected outcome differences in symptoms between the two drugs, which included more hot flashes with tamoxifen treatment and more vaginal problems and musculoskeletal complaints with anastrozole treatment.
"The NSABP B-35 trial enrolled 3,104 postmenopausal women with DCIS that was hormone receptor-positive, and the primary endpoint was to determine whether anastrozole was superior to tamoxifen. Anastrozole was found to be slightly but significantly better than tamoxifen in terms of breast cancer-free interval, and it was most beneficial in women younger than 60 years. There was no overall survival difference between the two treatments," said Patricia A. Ganz, MD, distinguished professor at UCLA schools of Medicine & Public Health and the Jonsson Comprehensive Cancer Center at UCLA. "The secondary endpoints of the trial were QOL and symptom outcomes, measured as PRO. Because these two drugs have different side-effect profiles it was important to hear from women about their experiences to add that information to decision making."
PRO data is information obtained from each patient participating in the trial about her experience with the drug in terms of physical and emotional functioning (QOL) and various symptoms such as hot flashes, vaginal dryness, muscle and joint aches and pains (symptoms), Ganz explained. Since this was a double-blind trial, assessments were done without the bias of knowing what medication the women were taking, she added. "The information from this trial is important for women diagnosed with DCIS in the future who may be deciding which medication to take, along with their doctors," Ganz said.
Ganz and colleagues used data from 1,193 patients enrolled in the PRO portion of the NSABP B-35 trial. QOL and symptom data were collected at baseline prior to randomization to anastrazole or tamoxifen, every six months during the five years of treatment, and 12 months after treatment. QOL was measured using the SF-12 Physical Component Summary and Mental Component Summary. Symptoms were measured using the BCPT Symptom Checklist and other standardized methods. Patients were grouped into those younger than 60 years or those 60 years or older.
Five years after treatment, there were no differences in QOL outcomes. However, the severity of hot flashes was greater in those who received tamoxifen than those who received anastrozole, and this experience varied over time; the severity of musculoskeletal pain at 6-month to 24-month timepoints and vaginal problems was greater in those who received anastrozole than those who received tamoxifen. Sexual functioning was slightly worse for those who received anastrozole compared with those who received tamoxifen. There was no worsening of physical or emotional health and depression with either drug, and overall, both drugs were found to be safe, according to Ganz. All symptoms were worse in women younger than 60 years than those 60 years or older, she added.
"Both of these drugs are excellent and can reduce the risk for breast cancer recurrence. Physicians and patients need to use this information along with the main trial outcomes to choose the optimal treatment for each woman. This is part of personalized or precision medicine," Ganz said.
This study was supported by the National Cancer Institute and AstraZeneca. Ganz declares no conflicts of interest.
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Title: Patient-reported outcome (PRO) results, NRG Oncology/NSABP B-35: A clinical trial of anastrozole (A) vs tamoxifen (tam) in postmenopausal patients with DCIS undergoing lumpectomy plus radiotherapy
Authors: Patricia A Ganz1,2, Reena S Cecchini1,3, Thomas B Julian1,4, Richard G Margolese1,5, Joseph P Costantino1,6, Laura A Vallow1,7,Kathy S Albain1,8, Pat W Whitworth1,9, Mary E Cianfrocca1,10, Adam Brufsky1,11, Howard M Gross1,12, Gamini S Soori1,13, Judith O Hopkins1,14, Lou Fehrenbacher1,15, Keren Sturtz1,16, Timothy F Wozniak1,17, Thomas E Seay1,18, Eleftherios P Mamounas1,19 and Norman Wolmark1,4. 1NSABP/NRG Oncology; 2UCLA Schools of Medicine and Public Health and Jonsson Comprehensive Cancer Center; 3University of Pittsburgh; 4Allegheny Cancer Center at Allegheny General Hospital; 5Jewish General Hospital, McGill University; 6NRG Oncology Statistics and Data Management Center (SDMC); 7Mayo Clinic; 8Loyola University Chicago Cardinal Benardin Cancer Center; 9Nashville Breast Center; 10Fox Chase and Northwestern (ECOG); 11Magee-Women's Hospital,University of Pittsburgh; 12Dayton NCORP; 13Missouri Valley Cancer Consortium; 14Novant Health; 15Kaiser Permanente Northern California; 16Colorado Cancer Research Program; 17Christiana Care CCOP; 18Atlanta Regional CCOP and 19UF Health Cancer Center at Orlando Health.
Background: The clinical results of NSABP B-35, phase III trial comparing 1 mg/day A to 20 mg/day tam, each given for 5 years, were reported at ASCO 2015. B-35 demonstrated a statistically significant benefit in breast cancer free interval for women assigned to A, primarily in women <60 years. A secondary endpoint of B-35 was quality of life (QOL) and symptom (SX) outcomes in the two treatment groups. The primary hypotheses of the PRO study were that there would be no differences in QOL between the two treatments, and that patients receiving A would report higher rates of hot flashes compared to patients receiving tam. Other SX comparisons were secondary endpoints.
Methods: QOL and SX were assessed at baseline (prior to randomization), and every 6 months thereafter for 5 years of treatment and in the following 12 months. QOL was measured with the SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS). SX were measured with selected scales from the BCPT symptom-checklist, and other standardized instruments. Stratification was by age (<60 v ³60) as in the main trial. Study hypotheses and endpoints were examined by comparing PROs in the two treatment arms using a mixed model for repeated measures analysis with adjustment for the baseline scores, time point and age category, using an intention-to-treat principle and including only patients who completed the baseline and at least one follow-up questionnaire. Patients with protocol events were censored. Only data through 60 months are reported here. The accrual goal for the sub-study was 1,150 consecutive patients.
Results: Between January 6, 2003 and June 15, 2006, a total of 3,104 patients were entered and randomly assigned to NSABP Protocol B-35. Accrual to the PRO study of B-35 closed on December 28, 2004, at which time 1,275 patients were entered, with 1,193 patients included in this analysis. There were no medical or demographic differences between patients assigned to A or tam in the PRO sub-study, and they reflected the characteristics of the parent trial. Adherence to data collection across the 60 months was 87%. There were no significant differences in QOL outcomes by treatment for the PCS (p=0.16) or the MCS (p=0.38). SX subscales: hot flash scale was greater in tam group and this difference varied over time (p=0.001); musculoskeletal pain was significantly greater in A group for time points 6-24 months (all p<.001); vaginal problems were greater in A group (p=0.03). Hot flash and vaginal problems were significantly worse in women <60 years. Additional SX outcomes (depression, fatigue, sexual function) will be reported at presentation.
Conclusion: In this large, double-blind, placebo-controlled trial comparing A to tam in patients with DCIS, there was no significant difference in QOL between the two treatments. However, there were important treatment differences in SX outcomes, which should be considered as part of treatment decision-making discussions, along with the clinical breast cancer outcome results.
Support: CA-180868, 180822, 189867, 196067, 114732; AstraZeneca Pharmaceuticals LP.
This research will be presented at a press conference at the 2015 San Antonio Breast Cancer Symposium, moderated by SABCS Co-director Kent Osborne, MD, director of the Dan L Duncan Cancer Center at Baylor College of Medicine, Friday, Dec. 11, 7:30 a.m. CT in Room 217D of the Henry B. Gonzalez Convention Center. Reporters who cannot attend the press conference in person can call in using the following information:
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To interview Patricia Ganz, contact Julia Gunther at firstname.lastname@example.org or 267-250-5441.