|Canadian Cancer Trials Group MA.26 (SWOG 9927)- Randomized Trial of Post-Mastectomy Radiotherapy in Stage II Breast Cancer in Women with One to Three Positive Axillary Nodes
The Radiation Therapy Oncology Group 9804 study identified good-risk patients with ductal carcinoma in situ (DCIS), a breast cancer diagnosis found frequently in mammographically detected cancers, to test the benefit of radiotherapy (RT) after breast-conserving surgery compared with observation.
This prospective randomized trial (1998 to 2006) in women with mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins ≥ 3 mm, compared RT with observation after surgery. The study was designed for 1,790 patients but was closed early because of lower than projected accrual. Six hundred thirty-six patients from the United States and Canada were entered; tamoxifen use (62%) was optional. Ipsilateral local failure (LF) was the primary end point.
The authors concluded that in this good-risk subset of patients with DCIS, with a median follow-up of 7 years, the LF rate was low with observation but was decreased significantly with the addition of RT. Longer follow-up is planned because the timeline for LF in this setting seems protracted.
McCormick B, Winter K, Hudis C, Kuerer HM, Rakovitch E, Smith BL, Sneige N, Moughan J, Shah A, Germain I, Hartford AC, Rashtian A, Walker EM, Yuen A, Strom EA, Wilcox JL, Vallow LA, Small W, Pu AT, Kerlin K, White J. RTOG 9804: A Prospective Randomized Trial for Good-Risk Ductal Carcinoma In Situ Comparing Radiotherapy With Observation. J Clin Oncol 33: 709-15, 2015.
Canadian Cancer Trials Group MAC.11 (SWOG 0221) - A Phase III Trial of Continuous Schedule AC + G vs Q2 Week Schedule AC, Followed by Paclitaxel Given Either Every 2 Weeks or Weekly for 12 Weeks as Post-Operative Adjuvant Therapy in Node-Positive or High-Risk Node-Negative Breast Cancer
The purpose of this study was to determine the optimal dose and schedule of anthracycline and taxane administration as adjuvant therapy for early-stage breast cancer.
A 2 x 2 factorial design was used to test two hypotheses: (1) that a novel continuous schedule of doxorubicin-cyclophosphamide was superior to six cycles of doxorubicin-cyclophosphamide once every 2 weeks, and (2) that paclitaxel once per week was superior to six cycles of paclitaxel once every 2 weeks in patients with node-positive or high-risk node-negative early-stage breast cancer. With 3,250 patients, a disease-free survival (DFS) hazard ratio of 0.82 for each randomization could be detected with 90% power with two-sided α = .05. Overall survival (OS) was a secondary outcome.
Interim analyses crossed the futility boundaries for demonstrating superiority of both once-per-week regimens and once-every-2-weeks regimens. The author concluded that patients achieved a similar DFS with any of these regimens. Subset analysis suggests the hypothesis that once-every-2-weeks dosing may be best for patients with hormone receptor?negative/HER2-negative tumors.
Budd GT, Barlow WE, Moore HCF, Hobday TJ, Stewart JA, Isaacs C, Salim M, Cho JK, Rinn KJ, Albain KS, Chew HK, Burton GV, Moore TD, Srkalovic G, McGregor BA, Flaherty LE, Livingston RB, Lew DL, Gralow JR, Hortobagyi GN. SWOG S0221: A Phase III Trial Comparing Chemotherapy Schedules in High-Risk Early-Stage Breast Cancer. J Clin Oncol 33: 58-64, 2015.
Canadian Cancer Trials Group MAC.8 (NSABP B37) - A Randomized Clinical Trial of Adjuvant Chemotherapy for Radically Resected Loco-Regional Relapse of Breast Cancer
The aim of this study was to establish whether adjuvant chemotherapy improves the outcome of patients with isolated locoregional recurrences (ILRR) of breast cancer who hav pragmatic, open-label, randomized trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Patients were randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival.
The results of the study showed that adjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative.
Aebi S, Gelber S, Anderson SJ, Lang I, Robidoux A, Martin M, Nortier JWR, Paterson AHG, Rimawi MF, Canada JMB, Thurlimann B, Murray E, Mamounas EP, Geyer Jr CE, Price KN, Coates AS, Gelber RD, Rastogi P, Wolmark N, Wapnir IL. Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial. The Lancet Oncology 15: 156-63, 2014.