NAB-Paclitaxel Improves Disease-Free Survival in Early Breast Cancer: GBG 69–GeparSepto

Abstract

PURPOSE The GeparSepto trial demonstrated that weekly nanoparticle albumin-bound (NAB)–paclitaxel significantly improves the pathologic complete remission rate compared with weekly solvent-based (sb) paclitaxel followed by epirubicin plus cyclophosphamide as neoadjuvant treatment in patients with primary breast cancer (BC). Here, we report data on long-term outcomes. METHODS Patients with histologically confirmed primary BC were randomly assigned in a 1:1 ratio to 12 times weekly NAB-paclitaxel 150 mg/m2 (after study amendment, 125 mg/m2) or weekly sb-paclitaxel 80 mg/m2 followed in both arms by four times epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks. Patients with human epidermal growth factor receptor 2 (HER2)-positive BC received dual antibody treatment with trastuzumab (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks) and pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks) concurrently to chemotherapy and continued for 1 year. RESULTS A total of 1,206 patients started treatment, 606 with NAB-paclitaxel and 600 with sb-paclitaxel. After a median follow-up of 49.6 months (range, 0.5 to 64.0 months), 243 invasive disease–free survival (iDFS) events were reported (143 in the sb-paclitaxel and 100 in the NAB-paclitaxel arm). At 4 years, overall patients treated with NAB-paclitaxel had a significantly better iDFS compared with sb-paclitaxel (84.0% v 76.3%; hazard ratio, 0.66; 95% CI, 0.51 to 0.86; P = .002), whereas overall survival did not significantly differ between the two treatment arms (89.7% v 87.2%, respectively; hazard ratio, 0.82; 95% CI, 0.59 to 1.16; P = .260). Long-term follow-up of the treatment-related peripheral sensory neuropathy (PSN) showed a significant decrease of the median time to resolve PSN after NAB-paclitaxel 125 mg/m2 compared with NAB-paclitaxel 150 mg/m2. CONCLUSION The significantly higher pathologic complete response rate with NAB-paclitaxel translated into a significantly improved iDFS in patients with early BC as compared with sb-paclitaxel. PSN improved much faster under NAB-paclitaxel 125 mg/m2 compared with NAB-paclitaxel 150 mg/m2.

Neoadjuvant Treatment for Triple Negative Breast Cancer: Recent Progresses and Challenges

“…When nab-paclitaxel was used instead of paclitaxel in phase III trial, the improvement of pCR was not statistically significant, showing pCR 41.3% with nab-paclitaxel vs. 37.7% with paclitaxel in the TNBC group (OR 0.85; 90% CI, 0.49-1.45) [52]. The GeparSepto trial that included about 20% of TNBC demonstrated significantly higher pCR in nab-paclitaxel subgroup than in the paclitaxel subgroup (48% vs. 26%, p = 0.00027) [53]. Additionally, nab-paclitaxel showed superior pCR when given with carboplatin as compared with gemcitabine [44].…”

Modeling of Nanotherapy Response as a Function of the Tumor Microenvironment: Focus on Liver Metastasis

“…A number of HMW-based therapeutic strategies has been clinically approved and proposed for the therapy of advanced breast cancer, pancreatic ductal denocarcinoma and other tumors, including albumin-bound drug conjugates, such as nanoalbumin bound paclitaxel, nAb-PTX or Abraxane R (Blomstrand et al, 2019;Li and Kwon, 2019;Untch et al, 2019), monoclonal antibodies (mAb), such as anti-HER2 mAb trastuzumab (Figueroa-Magalhaes et al, 2014) or anti-EGFR mAb, cetuximab (Huang and Buchsbaum, 2009), and genetic materials, including siRNA, mRNA, and aptamers (Kang et al, 2015;Ngamcherdtrakul and Yantasee, 2019). In liver metastatic lesions with low vascularization patterns, these potent therapeutics are unable to be transported deeply enough into the lesions prior to their clearance from circulation.…”

Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes

“…The improvement of pCR rate was mainly observed among the 275 patients affected by TNBC (48% with nab-paclitaxel versus 26% with standard paclitaxel). Noteworthy, a significant invasive DFS benefit was reported in the TNBC subgroup who achieved pCR, supporting the value of pCR as the surrogate endpoint for long-term outcomes in this population [87].…”