Early breast cancer

Updates from ESMO: Benefit of Extended Adjuvant Neratinib in HER2-Positive Early Breast Cancer Sustained

The 2017 European Society for Medical Oncology (ESMO) Congress was held 8 – 12 September in Madrid, Spain. For the first time, this conference was organized in partnership with the European Association for Cancer Research (EACR). The congress theme was “integrated science into oncology for a better patient outcome”. Almost 24000 delegates from around the world gathered to discuss emerging cancer research innovations and the latest advances in cancer management. As in the past two years, immunotherapy and targeted therapy were in the spotlight at this congress. Over the next weeks, our prIME LINES™ editions will highlight some of the important presented abstracts that may impact clinical practice.

Among the abstracts in early breast cancer, the results of the five-year analysis of the phase III ExteNET trial were presented at a proffered paper session by Miguel Martin, MD, PhD (Hospital Gregorio Marañon, Madrid, Spain). Results confirmed continued significant benefit of extended adjuvant therapy with neratinib therapy in patients with early HER2-positive breast cancer. The ExteNET trial compared one year of the pan-HER tyrosine kinase inhibitor (TKI) neratinib (240 mg daily) to placebo in 2840 patients with HER2-positive early breast cancer who had completed standard one-year treatment with trastuzumab-based adjuvant therapy. In the previously reported two-year analysis, neratinib demonstrated a significant improvement in invasive disease free survival (iDFS) compared to placebo (HR 0.67, P = .0091). According to results of the preplanned five-year analysis presented in Madrid this year, the benefit was sustained. At a median follow-up of 5.2 years, the estimated rates of iDFS in the intent-to-treat population were 90.2% with neratinib and 87.7% with placebo (2.5 absolute benefit, HR 0.73, P = .008). Greatest benefit of neratinib was seen in the subgroup of patients who had hormone receptor (HR)–positive disease. In these patients, iDFS at five years was 91.2% with neratinib compared to 86.8% with placebo (4.4% absolute benefit, HR 0.60, P = .002). In addition, patients who started neratinib within one year of completing trastuzumab had better iDFS than those who received neratinib more than one year after completion of trastuzumab (3.2% absolute benefit, HR 0.70, P = .006). Overall survival data are not yet mature and are expected in 2019. Importantly, at five years there was no evidence of long-term toxicity or long-term consequences from neratinib-associated diarrhea.

In her discussion, Hope S. Rugo, MD, FACP (University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California, United States), indicated that the consistency of these data with previously reported trial results, coupled with the improved toxicity profile seen with antidiarrheal prophylaxis, support inclusion of neratinib in the treatment paradigm for HER2-positive early breast cancer; particularly for patients who have high-risk, HR-positive disease.


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