Sequential victories.

Top Line: In 2013 we learned that trastuzumab (aka Herceptin) throughout versus sequential to neoadjuvant chemo didn’t improve pathologic complete response (pCR) rates. But is that a good enough surrogate for survival?
The Study: The phase 3 ACOSOG 1041 trial asked if more neoadjuvant trastuzumab meant more pCRs at time of surgery. According to the initial pub: it didn’t. This multi-institutional US trial randomized 282 women with HER2(+) breast cancer of at least 2 cm to [1] neoadjuvant paclitaxel → epirubicin/ cyclophosphamide/ 5FU (ECF) with trastuzumab throughout versus [2] sequential ECF alone → paclitaxel/trastuzumab. As alluded to before, the pCR rates were both no different and amazingly high at 50% and 53%, respectively. This week brings us final reporting of disease-free and overall survival outcomes. Recurrences and death, respectively, occurred in 22 (15%) and 12 (8%) of 142 with extended concurrent trastuzumab and 18 (13%) and 8 (6%) of 138 with sequential trastuzumab. What’s the real difference between these two arms? The first (concurrent) arm required 24 weeks of neoadjuvant trastuzumab while the second (sequential) arm required only 12 weeks. Sounds like a big difference until you realize they all received additional post-op adjuvant trastuzumab to complete a total of 12 months of systemic therapy.
Bottom Line: Less may be more when it comes to duration of HER2-targeted therapy for early-stage HER2(+) breast cancer. And pCR is remains a solid surrogate for more clinically meaningful survival outcomes. | Buzdar, JAMA Oncol 2018


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