Randomized Trial of Standard Adjuvant Chemotherapy Regimens Versus Capecitabine in Older Women With Early Breast Cancer: 10-Year Update of the CALGB 49907 Trial

Abstract

PURPOSE Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician’s choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer–specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor–negative patients (HR, 0.66; P = .02), but not among hormone receptor–positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor–negative disease. Competing risks in this older population dilute overall survival benefits.

The role of capecitabine-based neoadjuvant and adjuvant chemotherapy in early-stage triple-negative breast cancer: a systematic review and meta-analysis

“…There were five [ 14 , 17 – 19 , 21 ] and four [ 15 , 16 , 20 , 22 ] studies involving the addition or replacement of capecitabine to neoadjuvant or adjuvant chemotherapy, respectively. From the available data of TNBC, there were 1373 capecitabine combined and 1356 capecitabine-free cases in the group with the addition of capecitabine, and 384 capecitabine combined and 357 capecitabine-free cases in the group with the replacement of capecitabine.…”

“…There were seven [ 14 – 19 , 21 , 22 ] and one [ 20 ] studies that used capecitabine as adjuvant and neoadjuvant chemotherapy, respectively, and one study that used capecitabine as both neoadjuvant and adjuvant chemotherapy [ 19 ]. From the available data of TNBC, there were 1757 cases of adjuvant chemotherapy with capecitabine and 1713 cases of adjuvant chemotherapy without capecitabine, along with 448 cases of neoadjuvant chemotherapy with capecitabine and 428 cases of neoadjuvant chemotherapy without capecitabine.…”

Adjuvant chemotherapy and survival in women aged 70 years and older with triple-negative breast cancer: a Swedish population-based propensity score-matched analysis

“…The 10-year update of the CALBG 49907 trial confirmed the superiority of standard adjuvant chemotherapy in improving BCSS and recurrence-free survival, but no significant improvement was found in OS, probably due to competing risks of death diluting the benefit in an older population. 30 The follow-up trial also used modest chemotherapy regimens (ie, four courses of doxorubicin and cyclophosphamide or six courses of CMF).…”

Neoadjuvant Immune-Checkpoint Blockade in Triple-Negative Breast Cancer: Current Evidence and Literature-Based Meta-Analysis of Randomized Trials

“…However, no evidence of significantly improved five-year OS was observed for patients allocated to the intervention arm (HR, 0.74, p = 0.203) [ 30 ]. Even though results from clinical trials regarding the implementation of capecitabine in early TNBC were not always consistent [ 31 , 32 , 33 ], routine clinical care of TNBC not achieving pCR after neoadjuvant chemotherapy often embraces adjuvant treatment with capecitabine. Moreover, a recent meta-analysis presented at the 2019 San Antonio Breast Cancer Symposium highlighted more pronounced, significant benefits in terms of DFS and OS from the addition of capecitabine to neoadjuvant chemotherapy in the TNBC subtype [ 34 ].…”