NeoSphere is a phase II trial in which 417 women with newly diagnosed HER2-positive, operable, locally advanced or inflammatory early breast cancer were randomized to four different neoadjuvant therapy arms. Surgery was followed by a one-year adjuvant therapy phase. Data from the 2015 ASCO Congress now confirm the long-term benefit of adding pertuzumab to docetaxel and trastuzumab.
The addition of pertuzumab to docetaxel and trastuzumab results in significantly more complete breast remissions (16.8% increase, p=0.0141). This is shown by data from NeoSphere, which was already published in 2012 [1]. This parameter is defined as the complete absence of detectable tumor tissue in the breast at the time of surgery. Complete remissions in breast and axilla also increased by 17.8% with the addition (39.3% vs. 21.5%, p=0.0063). Side effects did not occur more frequently.
Three-year survival data from the study have now been presented at the 2015 ASCO Congress:
- Three years after surgery, 92% of patients who received pertuzumab, trastuzumab, and docetaxel were alive without progression, compared with 85% in the other group (trastuzumab and docetaxel). This corresponds to a risk reduction in disease-free survival of 40%.
- Three years after randomization, 90% of the first group lived progression-free, and 86% of the second group (risk reduction in progression-free survival of 31%).
- In the remaining two arms studied (pertuzumab and trastuzumab; pertuzumab and docetaxel), the rates for disease-free survival were 88% and 84%, and for progression-free survival were 81% and 82%.
- The risk of progression or death was significantly reduced in those patients who achieved complete remission. Compared with study participants who missed the primary endpoint, the hazard ratio in disease-free survival here was 0.68 (95% CI 0.36-1.26) and in progression-free survival 0.54 (95% CI 0.29-1.00). This supports the notion that improvements in long-term outcome are associated with the achievement of complete remission.
Conclusion of the follow-up
Overall, the long-term data suggest a benefit of adding pertuzumab to docetaxel and trastuzumab in the neoadjuvant therapy setting (administered four cycles over 12 weeks). This not only allows significantly more women to achieve complete remission, but also extends the time without progression or to death. This was with no change in adjuvant therapy, which in NeoSphere consisted of chemotherapy and trastuzumab in all four groups.
Based in part on the compelling data from NeoSphere, the EMA approved pertuzumab in combination with trastuzumab and chemotherapy for the neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory or early breast cancer at high risk of recurrence at the end of July 2015.
Source: ASCO Congress, May 29-June 2, 2015, Chicago.
Literature:
- Gianni L, et al: Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 2012 Jan; 13(1): 25-32.
InFo ONCOLOGY & HEMATOLOGY 2015; 3(9-10): 3.
