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. (12th July 2017)

• Record Type: Journal Article
• Authors: Martín, Miguel; Chacón, José I.; Antón, Antonio; Plazaola, Arrate; García‐Martínez, Elena; Seguí, Miguel A.; Sánchez‐Rovira, Pedro; Palacios, José; Calvo, Lourdes; Esteban, Carmen; Espinosa, Enrique; Barnadas, Agusti; Batista, Norberto; Guerrero, Angel; Muñoz, Montserrat; Romio, Estefania; Rodríguez‐Martín, César; Caballero, Rosalía; Casas, María I.; Rojo, Federico; Carrasco, Eva; Antolín, Silvia
• Is Part Of: Oncologist. Volume 22:Number 11(2017)
• Page Start: 1301
• Page End: 1308
• Publication Date: 2017-07-12
• Subjects: Estrogen receptor‐positive breast cancer -- Nanoparticle albumin‐bound Paclitaxel -- Neoadjuvant treatment -- Residual cancer burden -- Luminal breast cancer; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2017-0052
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract: Background: 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/m 2 ), 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). Abstract : The NABRAX study was designed to evaluate the antitumor activity and safety of single‐agent weekly nab‐paclitaxel as neoadjuvant treatment of estrogen receptor‐positive/HER2‐negative breast cancer patients. This article reports on the trial and efforts to define the role of this drug and biomarkers of activity in this particular subtype of breast cancer.