Does Sequential vs Concurrent Treatment Change Outcomes in HER2+ Breast Cancer?

Outcomes for patients with HER2-positive breast cancer did not differ when treated with sequential chemotherapy plus trastuzumab compared with a concurrent approach, according to a new phase III trial.

“The effectiveness of trastuzumab with chemotherapy in the neoadjuvant setting is evident; however, the cardiac safety of trastuzumab combined with anthracyclines has been questioned,” wrote study authors led by Kelly K. Hunt, MD, of the University of Texas MD Anderson Cancer Center in Houston.

The American College of Surgeons Oncology Group (ACOSOG) Z1041 trial was designed to compare two strategies for delivery of neoadjuvant chemotherapy and trastuzumab. It included 280 women with invasive, operable, HER2-positive breast cancer, randomized to receive either fluorouracil, epirubicin, and cyclophosphamide (FEC) every 3 weeks for 12 weeks followed by paclitaxel and trastuzumab for 12 weeks (arm 1, 138 patients), or the paclitaxel and trastuzumab combination for 12 weeks followed by FEC combined with trastuzumab (arm 2; 142 patients). Results of the study were published in JAMA Oncology.

The median age in the trial was 50 years, and most patients were white (82.9%); demographic characteristics were well balanced between the two arms. An earlier report from this trial found similar rates of pathologic complete response between arms 1 and 2 (56.5% vs 54.2%).

There were 18 recurrences in the arm 1 patients receiving sequential therapy, as well as two second primary cancers; in arm 2, there were 22 recurrences and three second primary cancers. Disease-free survival rates did not differ between the two groups, with a stratified hazard ratio (HR) comparing arm 2 vs arm 1 of 1.02 (95% CI, 0.56–1.83; P = .96).

Eight patients in arm 1 and 12 patients in arm 2 died during the study period. Five arm 1 patients and seven arm 2 patients died due to the initial cancer, while other known causes of death included drug overdose, second primary cancer, and respiratory failure. Overall survival also was no different between the groups, with a stratified HR of 1.17 (95% CI, 0.48–2.88; P = .73).

“Concurrent administration of trastuzumab with FEC was not found to offer additional benefit and is not warranted,” the authors concluded.

However, Robert E. Coleman, MD, of the University of Sheffield in the United Kingdom, who was not involved with the research, said the finding was not surprising given the small total number of recurrences in the trial. “Interesting study, but underpowered to adequately compare sequential vs concomitant treatment,” he told Cancer Network. “Clinicians will continue to give concomitant treatment on the basis of other studies suggesting better efficacy and to enable treatment to be completed sooner.”