Latest Trastuzumab debate throws down a challenge to the Federal Government

Dr Goldhirsch (Director of the Department of Medicine at the European Institute of Oncology, Milan, Italy, and Chief Physician at the Oncology Institute of Southern Switzerland) presented the results from the NOAH (NeOAdjuvant Herceptin) trial to delegates at the 2008 San Antonio Breast Cancer Symposium last week.

Researchers from the NOAH (NeOAdjuvant Herceptin) trial have published the first data supporting the use of neoadjuvant trastuzumab in combination with chemotherapy in locally advanced HER2 positive breast cancer.¹ Trastuzumab is currently used as adjuvant treatment in combination with a taxane for early breast cancer and metastatic breast cancer with or without chemotherapy.

NOAH is an international Phase III trial evaluating efficacy and safety of an anthracycline- and paclitaxel- containing chemotherapy followed by cyclophosphamide, methotrexate and 5-fluorouracil, with or without trastuzumab in women with newly diagnosed HER2-positive locally advanced breast cancer.¹ Women with hormone receptor positive cancer also received adjuvant tamoxifen.¹

Results were compared with a parallel observational cohort of patients with HER2-negative locally advanced breast cancer receiving the same chemotherapy regimen with no trastuzumab.¹ The trial recruited 327 women to receive the same chemotherapy regimen with or without trastuzumab. 228 HER2 positive women randomised to a trastuzumab arm (n = 115) and a chemotherapy without trastuzumab arm (n=113), and ninety-nine HER2-negative women received the same chemotherapy regimen without trastuzumab.¹ The primary end point was event free survival (EFS) with secondary endpoints being pathological complete response, overall response rate, safety and tolerability.¹

While event-free survival results are still maturing, preliminary data at 3 years shows EFS was significantly increased in the trastuzumab group compared the group receiving with chemotherapy alone (70% vs 53.3% respectively).¹ What was particularly interesting was the very high rate of pathological complete response in the women receiving trastuzumab (39%) compared to 20% of women who did not receive trastuzumab.¹ Treatment was well tolerated with acceptable cardiac safety.² The most common serious adverse event was neutropenia (8% with trastuzumab vs 4% without).² Nineteen women crossed over from the chemotherapy only arm to the trastuzumab arm during treatment.¹

The data from this trial establishes neoadjuvant trastuzumab with chemotherapy as a standard treatment option for women with HER2-positive locally advanced breast cancer.¹

The question is, will the federal government take heed of these results and fast-track the availability of trastuzumab for patients with locally advanced breast cancer so that it can be used in the neoadjuvant setting?

References

1. Gianni L, Eiermann V, Semiglazov V, Manikhas GM, Lluch A, Tjulandin S, Feyereislova A, Valagussa P, Baselga J. Neoadjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer: primary efficacy analysis of the NOAH trial. [Powerpoint presentation]. Presented at the San Antonia Breast Cancer Symposium. Retrieved December 16, 2008, from http://sabcs08.m2usa.com/previewer.html 
2. Gianni L, Semiglazov V, Manikhas GM,  Eiermann V, Lluch A, Tjulandin S, Feyereislova A, Valagussa P, Baselga J. Neoadjuvant trastuzumab in locally advanced breast cancer (NOAH): Antitumour and safety analysis. Journal of Clinical Oncology. 2007 ASCO Annual Meeting Proceedings Part 1. Vol 25, No18S (June 20 Supplement):532.