Abstract P5-15-03: nab-paclitaxel + carboplatin or gemcitabine vs gemcitabine/carboplatin as first-line treatment for patients with triple-negative metastatic breast cancer: Results from the randomized phase 2 portion of the tnAcity trial
Authors: Yardley D , Coleman R , Conte P , Cortes J , Brufsky A , Shtivelband M , Young R , Bengala C , Ali H , Eakel J , Schneeweiss A , de la Cruz Merino L , Wilks S , O'Shaugnessy J , Glück S , Li H , Beck R , Barton D , Harbeck N 
Published: March 2017

Abstract
Background: nab-Paclitaxel (nab-P)–containing regimens have demonstrated efficacy and safety in triple-negative breast cancer (TNBC). In the absence of a standard of care for metastatic (m) TNBC, tnAcity evaluated the efficacy and safety of 3 common chemotherapy combination regimens: nab-P + carboplatin (nab-P/C) or gemcitabine (nab-P/G) vs G/C as first-line treatment (Tx) for patients (pts) with mTNBC based on a ranking algorithm of efficacy and safety. Results of the phase 2 portion are reported here.
Methods: Pts with pathologically confirmed mTNBC, no prior cytotoxic chemotherapy for metastatic disease, and no brain metastases were enrolled. Pts received (1:1:1) nab-P 125 mg/m2 + C AUC 2, nab-P 125 mg/m2 + G 1000 mg/m2, or G 1000 mg/m2 + C AUC 2, all given on d 1 and 8 every 3 weeks. The phase 2 primary endpoint was investigator-assessed progression-free survival (PFS); secondary endpoints included overall response rate (ORR), overall survival (OS), percentage of pts initiating cycle 6 receiving doublet therapy, and safety.
Results: 191 pts were included in the phase 2 portion. Median age was 55, 53, and 59 years in the nab-P/C, nab-P/G, and G/C groups, respectively. Overall, 98% of pts had an ECOG PS of 0 - 1, 83% were white, and 48% were treated in North America. Most pts (81%) had relapsed disease. Median Tx duration was 25, 18, and 20 weeks, and 47%, 33%, and 52% of pts had ≥ 1 dose reduction for both agents in the nab-P/C, nab-P/G, and G/C groups, respectively. Key efficacy and safety results are summarized in the table. PFS was significantly longer with nab-P/C vs either nab-P/G or G/C (median, 7.4 vs 5.4 mo, P = 0.03 and 7.4 vs 6.0 mo, P = 0.02). Overall, 179 pts discontinued Tx; of these, 55% discontinued due to progression and 16% due to adverse events (AEs). Grade ≥ 3 AEs in ≥ 10% of pts were mainly hematologic. The rank sum of the algorithm for 5 key weighted efficacy and safety endpoints favored nab-P/C.
Table 1 nab-P/Cnab-P/GG/CEfficacyn = 64n = 61n = 66PFS, median, mo7.4a5.4b6.0ORR, %71.937.743.9OS, median, mo16.411.913.7Pts initiating cycle 6 with a doublet, %64.155.750.0Safetyn = 64n = 60n= 64Myelosuppression-related events, %c53.141.767.2Pts discontinuing all Tx due to AE, %18.820.021.9Serious TEAEs, %29.736.737.5Grade ≥ 3 AEs, %Neutropenia40.633.348.4Anemia7.88.315.6Thrombocytopenia4.73.314.1Peripheral neuropathy4.75.01.6Deaths due to TEAE, n (%)1 (2)2 (3)2 (3)a P = 0.03 vs nab-P/G; P = 0.02 vs G/C; b P = 0.85 vs G/C; c Including grade ≥ 3 neutropenia, thrombocytopenia, anemia, bleeding, febrile neutropenia, or red blood cell/platelet transfusion.
Conclusions: In this phase 2 study, nab-P/C demonstrated a statistically significant longer PFS and a better risk/benefit profile vs nab-P/G or G/C as first-line Tx in pts with mTNBC. These data demonstrate nab-P/C efficacy in mTNBC and address a relevant question around a nab-P/C chemotherapy backbone for this difficult-to-treat tumor type. Further studies are warranted in the context of immunotherapies and targeted agents. NCT01881230.
Citation Format: Yardley D, Coleman R, Conte P, Cortes J, Brufsky A, Shtivelband M, Young R, Bengala C, Ali H, Eakel J, Schneeweiss A, de la Cruz Merino L, Wilks S, O'Shaugnessy J, Glück S, Li H, Beck R, Barton D, Harbeck N. nab-paclitaxel + carboplatin or gemcitabine vs gemcitabine/carboplatin as first-line treatment for patients with triple-negative metastatic breast cancer: Results from the randomized phase 2 portion of the tnAcity trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-15-03.