Abstract P1-12-06: UCBG intergroup: 3-years efficacy results of the Unicancer-PACS08 trial including poor prognosis patients treated with docetaxel or ixabepilone in adjuvant setting
Authors: Campone M , Lacroix-Triki M , Roca L , Spielmann M , Wildiers H , Cottu P , Kerbrat P , Levy C , Mayer F , Bachelot T , Wiston T , Eymard J-C , Uwer L , Machiels J-P , Verhoeven D , Jaubert D , Facchini T , Orfeuvre H , Canon J-L , Asselain B , Lemonnier J , Roché H 
Published: May 2016

Background: Ixabepilone, an epothilone B analog, has demonstrated single-agent activity in metastatic and neoadjuvant settings. The PACS08 trial aimed to compare adjuvant FEC100-Docetaxel regimen to FEC100-Ixabepilone in poor prognosis early breast cancer (BC) composed of patients presenting with triple-negative (TN) [i.e. estrogen receptor (ER)-/progesterone receptor (PR)-/HER2-] or ER+/PR-/HER2- tumor, which are subgroups significantly associated with worse prognosis.

Patients and methods: Between 2007 and 2010, 762 patients with unilateral TNBC (n=592, 78%) or node-positive ER+/PR-/HER2- BC (n=170, 22%) were enrolled. Recruitment was interrupted due to BMS decision to stop ixabepilone development in adjuvant setting. Main inclusion criteria were: age&lt;70 years, normal cardiac, hepatic, haematological and renal functions. Arm A: pts received 3 cycles of FEC100 (F and C, each at 500 mg/m2, E 100 mg/m2, every 3 weeks) followed by 3 cycles of Docetaxel (100 mg/m2 every 3 weeks); Arm B, Ixabepilone 40 mg/m2 replaced Docetaxel. Radiotherapy was mandatory after conservative surgery and endocrine therapy was given to ER+ pts. ER, PR and HER2 status were validated by a central pathology review on 754 cases and Immunohistochemical detection of Ki67, EGFR, cytokeratins (CK) 5/6 and 14, was performed on tissue microarray (TMA).

Results: Main pts characteristics were well balanced between the 2 arms. As of September 2014, the median follow-up was 36 months. The safety profile indicates that Docetaxel is more often associated to significant haematological toxicities whereas both neurotoxicities and haematological toxicities are reported in Ixabepilone arm. Log-Rank tests indicate no difference between two arms in terms of both DFS and OS (HR=1.2, 95%CI (0.864-1.728), p=0.256 and HR=1.8, 95%CI (0.751-1.855), p=0.473, respectively). Pathological analysis of the PACS08 collection showed that TNBC displayed significantly higher proliferative activity as shown by mitotic count and Ki67 index (p&lt;0.001). As compared to ER+/PR-/HER2- subgroup, TNBC showed distinct characteristics, and displayed a so-called basal-like phenotype in 80%. Further efficacy analyses are ongoing in order to study whether chemotherapy may have better prognosis according to pathological characteristics including tumor lymphocytic infiltrate. These additional data will be available for the SABCS2015 meeting.

Conclusions: Our results indicate that Ixabepilone doesn't show higher efficiency compared to Docetaxel in adjuvant setting in poor prognosis early breast cancer. We have an unusual biological collection associated to our clinical data which will allow us to correlate efficacy data to breast cancer subgroups. Other several translational researches are still ongoing.

Citation Format: Campone M, Lacroix-Triki M, Roca L, Spielmann M, Wildiers H, Cottu P, Kerbrat P, Levy C, Mayer F, Bachelot T, Wiston T, Eymard J-C, Uwer L, Machiels J-P, Verhoeven D, Jaubert D, Facchini T, Orfeuvre H, Canon J-L, Asselain B, Lemonnier J, Roché H. UCBG intergroup: 3-years efficacy results of the Unicancer-PACS08 trial including poor prognosis patients treated with docetaxel or ixabepilone in adjuvant setting. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-12-06.