San Antonio Breast Cancer Symposium 2014
GeparSepto: A Randomized Phase III Trial Comparing Nanoparticle based (nab) Paclitaxel with Solvent based paclitaxel as Part of Neoadjuvant Chemotherapy for Patients with Early Breast Cancer GBG 69.
Untch M, et al.
The role of neoadjuvant systemic therapy in primary operable breast cancer is increasing in both the research domain and in clinical practice. Within clinical research, the ability to study novel new agents or even conventional agents (such as in this study) with a surrogate end-point of pathological complete response (pCR) may allow for the earlier adoption into clinical practice (e.g. pertuzumab as part of a neoadjuvant regimen in HER2+ breast cancer in the US). Within standard clinical practice the proven role of neoadjuvant systemic therapy is to increase the operability rate, in particular the likelihood of breast conservation therapy in primary operable breast cancer. Taxanes are part of standard therapy in early stage breast cancer – both in the adjuvant and neoadjuvant setting. Nab-paclitaxel (albumin bound paclitaxel) has demonstrated efficacy in advanced stage breast cancer with the ability to deliver the taxane without a solvent (e.g. cremophor), and as such the ability to deliver higher doses of paclitaxel.
GeparSepto was a randomized phase III trial comparing weekly solvent based paclitaxel (80 mg/m2) to nab-paclitaxel (150 mg/m2) weekly x 12 weeks, followed by E90C600 q3 weeks x 4 cycles in both arms. The HER2+ cohort also received concurrent trastuzumab and pertuzumab with both the taxane and the anthracycline component. The primary end point of the study was pCR in both the breast and the lymph nodes (ypT0ypN0). 1,204 patients were enrolled from July 2012 – January 2014. After the first 400 patients were recruited, the nab-paclitaxel dose was reduced to 125 mg/m2 due to toxicities.
CARE Faculty Canadian Perspective:
· This is the first randomized phase III study comparing nab-paclitaxel to solvent based paclitaxel in early stage breast cancer.
· The results of GeparSepto suggest that weekly nab-paclitaxel is superior to weekly solvent based paclitaxel for the end-point of pCR. However the dose was modified from 150 mg/m2 to 125 mg/m2 due to significant toxicity. The true rate of ypT0ypN0 for nab-paclitaxel at 125 mg/m2 vs solvent based paclitaxel at 80 mg/m2 is not clear.
· The improved efficacy of nab-paclitaxel appears to be predominantly in triple negative breast cancer.
· However the rate of clinically significant (grade 3-4) peripheral sensory neuropathy with the doses of nab-paclitaxel used in GeparSepto is concerning (10%).
· Before nab-paclitaxel is incorporated into standard clinical practice knowledge regarding: 1) the relative dose intensity needed of nab-paclitaxel to achieve an improved pCR; 2) translation of the improved pCR leading to an improved efficacy outcomes (e.g. disease free survival) in GeparSepto; and 3) demonstration of resolution of the grade 3-4 peripheral sensory neuropathy to grade 0-1 is needed.
- CARE Breast Cancer Faculty
1. A Randomized Phase III Trial Comparing Nanoparticle based (nab) Paclitaxel with Solvent based paclitaxel as Part of Neoadjuvant Chemotherapy for Patients with Early Breast Cancer GBG 69 – GeparSept0. M Untch, C Jackisch, A Schneeweiss, et al, et al. San Antonio Breast Cancer Symposium 2014.