Abstract GS3-06: Long-term follow-up of CALGB 40502/NCCTG N063H (Alliance): A randomized phase III trial of weekly paclitaxel (P) compared to weekly nanoparticle albumin bound nab-Paclitaxel (NP) or ixabepilone (Ix) +/- bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer (MBC)
Authors: Rugo HS , Barry WT , Moreno-Aspitia A , Lyss A , Huebner L , Mayer EL , Naughton M , Layman RM , Carey LA , Somer RA , Toppmeyer D , Velasco M , Perez EA , Hudis CA , Winer E 
Published: February 2018

Abstract
Background: CALGB 40502/NCCTG N063H (Alliance) compared weekly NP or Ix to P; most patients received bevacizumab. Ix was inferior to P, and NP was not superior with a trend toward inferiority. Toxicity was increased in the experimental arms compared to P (Rugo et al, JCO 2015). We report long-term follow-up (FU) of this trial with an unplanned subset analysis in hormone receptor positive (HR+) and triple negative (TNBC) breast cancer.
Methods: Patients were randomized 1:1:1 to receive P (90 mg/m2), Ix (16 mg/m2) or NP (150 mg/m2) on a 3 week (wk) on, 1 wk off schedule, stratified by prior adjuvant taxane use and hormone receptor status. B was initially given to all patients, but became optional in 3/2011 and was added to stratification. The primary endpoint was progression-free survival (PFS); secondary endpoints included safety and overall survival (OS). With a target N=900 patients, the study was powered to detect a hazard ratio of 1.36 (median PFS 10 vs 13.6 months). Eligibility included no prior chemotherapy for MBC, &gt;12 mo from adjuvant P and measurable disease.
Results: 799 patients were randomized between 11/08 and11/11 (283 to P, 271 to NP, 245 to Ix); 98% received bevacizumab. 68% (546) had HR+ disease, 25% (201) had TNBC. Median FU is 5 years. Median PFS is unchanged at 10.8, 9.2 and 7.4 mo for P, NP and Ix with hazard ratios (95% CIs) of 1.13 (0.94-1.34) and 1.44 (1.2-1.72) for NP and Ix to P, respectively. Median OS was 27.1, 24.2 and 23.6 months for P, NP and Ix with hazard ratios of 1.10 (0.91-1.34) and 1.3 (1.07-1.57) for NP and Ix to P, respectively. The effects of NP vs P on PFS and OS were significantly modified by subtype (interaction p=0.0018 and 0.0073), whereas Ix vs P was unchanged (interaction p's &gt; 0.9, Table). More patients discontinued treatment due to adverse events in the experimental arms (14 vs 27 vs 23% for P, NP and Ix).
Table P (mo)NP (mo)NP to P; HR (95% CI)Ix (mo)Ix to P, HR (95% CI)TNBC, PFS6.47.40.79 (0.55-1.12)15.61.39 (0.99-1.96)3HR+, PFS12.29.61.29 (1.04-1.59)181.5 (1.21-1.86)3TNBC, OS15.3210.74 (0.51-1.07)215.11.28(0.9-1.82)4HR+, OS33.226.61.25 (0.99-1.58)225.41.35(1.07-1.714Interaction tests: 1. p=0.0018; 2. p=0.0073; 3. p=0.96; 4. p=0.92 mo: months; HR: hazard ratio··
Conclusion: In patients with chemotherapy-naive MBC, Ix was inferior to P for PFS, and P was better tolerated than either NP or Ix. In this retrospective subset analysis, Ix and NP were inferior to P in HR+ disease, with a suggestion of improved PFS and OS with NP in patients with TNBC. Further investigation is required to explain and validate the subtype specificity seen in this exploratory analysis.
Support: U10CA180820, U10CA180821, U10CA180882, U10CA180888. ClinicalTrials.gov Identifier: NCT00785291
Citation Format: Rugo HS, Barry WT, Moreno-Aspitia A, Lyss A, Huebner L, Mayer EL, Naughton M, Layman RM, Carey LA, Somer RA, Toppmeyer D, Velasco M, Perez EA, Hudis CA, Winer E. Long-term follow-up of CALGB 40502/NCCTG N063H (Alliance): A randomized phase III trial of weekly paclitaxel (P) compared to weekly nanoparticle albumin bound nab-Paclitaxel (NP) or ixabepilone (Ix) +/- bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS3-06.