Neoadjuvant Therapy with Weekly Nanoparticle Albumin‐Bound Paclitaxel for Luminal Early Breast Cancer Patients: Results from the NABRAX Study (GEICAM/2011‐02), a Multicenter, Non‐Randomized, Phase II Trial, with a Companion Biomarker Analysis

AbstractBackground.Nanoparticle albumin‐bound paclitaxel (nab‐Paclitaxel) is an alternative to standard taxanes for breast cancer (BC) treatment. We evaluated nab‐Paclitaxel efficacy as neoadjuvant treatment for early estrogen receptor‐positive (ER+), human epidermal growth factor receptor 2‐negative (HER2‐) disease.Materials and Methods.Women with ER+, HER2‐, stage II–III BC were treated preoperatively with four cycles of weekly nab‐Paclitaxel (150 mg/m2), 3 weeks on and 1 week off. We hypothesized that poor pathological response rate (residual cancer burden [RCB] III; Symmans criteria) would be ≤16%.Results.Eighty‐one patients with a median age of 47 years were treated; 64.2% were premenopausal, and 69% of tumors were stage II. Residual cancer burden III rate was 28.4% (95% confidence interval [CI]: 18.6%–38.2%), RCB 0+I (good response) rate was 24.7% (95% CI: 15.3%–34.1%) and RCB 0 (complete response) rate was 7.4% (95% CI: 1.7%–13.1%). Objective response rate by magnetic resonance imaging was 76.5% and rate of conversion to breast conserving surgery was 40.0%. The most frequent grade 3 and 4 toxicity was neutropenia (12.3% and 3.7% of patients, respectively), without any febrile neutropenia. Sensory neuropathy grade 2 and 3 were seen in 25.9% and 2.5% of patients, respectively. Tumor secreted protein, acidic, cysteine‐rich (SPARC) overexpression was significantly associated with RCB 0 (odds ratio: 0.079; 95% CI: 0.009–0.689; p = .0216).Conclusion.Despite failing to confirm an RCB III rate ≤16% in nab‐Paclitaxel‐treated patients, the RCB 0+I rate indicates a significant drug antitumor activity with low rates of grade 3–4 toxicity. Our exploratory biomarker analysis suggests a potential predictive role of complete response for SPARC. Confirmatory analyses are warranted, adapting dose and schedule to decrease peripheral neurotoxicity. (Trial registration: European Clinical Trials Database study number: 2011‐004476‐10; ClinicalTrials.gov: NCT01565499).Implications for Practice.The pathological response rate (residual cancer burden [RCB]; Symmans criteria) of nanoparticle albumin‐bound paclitaxel administered as neoadjuvant treatment for early estrogen receptor‐positive, human epidermal growth factor receptor 2‐negative disease was evaluated. Whereas poor response (RCB III) was 24.7%, similar to that for docetaxel, good response (RCB 0+I) reached 23.0%, far superior to the 13% for docetaxel, while keeping toxicity low. Exploratory biomarker analysis suggests secreted protein, acidic, cysteine‐rich overexpression in tumor cells as a potential predictor of complete response (RCB 0). Findings point to an encouraging single‐agent neoadjuvant treatment with low toxicity, which warrants future research and development.

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