P5-18-04: Safety Profile of Ixabepilone as Adjuvant Treatment for Poor Prognosis Early Breast Cancer: First Results of the Unicancer-PACS 08 Trial.
Authors: M Campone, M Spielmann, H Wildiers, P Cottu, P Kerbrat, C Levy, F Mayer, T Bachelot, T Winston, J-C Eymard, L Uwer, J-P Machiels, D Verhoeven, D Jaubert, T Facchini, H Orfeuvre, J-L Canon, B Asselain, L Roca, Triki M Lacroix, AL Martin, H Roche
Journal: Cancer Research (2011)

Abstract Purpose: PACS 01 trial demonstrated that the sequential adjuvant chemotherapy with FEC100 followed by docetaxel (D) significantly improves disease-free and overall survival in node-positive(N+) early breast cancer (BC). However, Triple negative (TN) and ER+/ PR-/HER2− subgroups are significantly associated to a worse prognosis even after adjunction of D. As Ixabepilone (Ixa) has notable preclinical and clinical activity in these subgroups, the PACS 08 trial aims to compare standard FEC100-D regimen to 3 cycles of FEC100 followed by 3 cycles of Ixa. We report the preliminary results of the toxicity profile. Patients and methods: Patients (pts) had localized resectable unilateral ER-/PR-/HER2− or ER+/PR-/HER2− BC. Main inclusion criteria were: age&amp;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 D (100 mg/m2 every 3 weeks); Arm B, Ixa 40 mg/m2 replaced D. Radiotherapy was mandatory after conservative surgery and endocrine therapy was given to ER+ pts. A 5% absolute difference in disease-free survival at 5 years is the main statistical end-point. Results: Between October 2007 and September 2010, 762 pts with TNBC or ER+/PR-/HER2− BC were enrolled. Recruitment was interrupted due to BMS decision to stop Ixa development in adjuvant setting. Main pts characteristics were well balanced between the 2 arms: median age 53 years, postmenopausal 57.8%, conservative surgery 68.4%, node positive 59.5%. A total of 755 pts were evaluable for safety. Treatment was completed for 93.4% and 86.1% of pts in arms A and B, respectively. During FEC100 sequence, toxicities were well balanced between the two arms. From cycle 4, whereas Gr3/4 sensory neurotoxicity (12pts; 3.5%) and thrombopenia (7pts; 2%) were reported in Ixa arm, none of these toxicities was reported in the D arm (p0.001). There were significantly more Gr3/4 neutropenia on day 21 in Ixa arm (13pts, 6.6% vs 4pts, 1.9%; p&amp;lt;10.005). No significant difference was observed for febrile neutropenia. Fewer cutaneous toxicities were observed in Ixa arm (2pts, 0.6% vs 10pts, 2.6%; p&amp;lt;0.05). No significant difference was observed neither for motor neurotoxicity or hepatic function between two arms. More pts discontinued treatment in Ixa arm compared to D arm (49pts (13%) vs 26pts (7%), p&amp;lt;0.05). Main reasons were Gr3/4 haematological adverse events (AE) and Gr3/4 neurotoxicities for Ixa arm and due to GR3/4 haematological AE for D arm. One non expected Gr4 bullous dermatitis was reported during the first Ixa cycle. 2 deaths due to septic shock occured in Ixa arm (both at cycle 4 for a 56- and a 66-year-old woman). However, according to the IDMC no obvious precipitating factor questioning the Ixa arm was identified. Conclusion: Our results indicate that D arm is more often associated to significant haematological toxicities, whereas both neurotoxicities and haematological toxicities are reported in the Ixa arm. Although significantly more pts discontinued treatment due to adverse events in Ixa arm compared to D arm, Ixa may still represent a promising therapeutic option for pts in the adjuvant setting especially for poor prognosis BC. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-04.