title: Balancing activity and tolerability of neoadjuvant paclitaxel- and docetaxel-based chemotherapy for HER2-positive early stage breast cancer: sensitivity analysis of randomized trials.
abstract: Paclitaxel and docetaxel represent the most adopted taxanes in the neoadjuvant treatment of HER2-positive breast cancer. Questions still remain with regard to their difference in terms of activity and tolerability. Events for pathological complete response (pCR), severe and febrile neutropenia (FN), and severe neurotoxicity were pooled by adopting a fixed- and random-effect model. A sensitivity analysis to test for the interaction between paclitaxel and docetaxel was accomplished. Absolute differences with 95% confidence intervals (CIs) and the number of patients needed to treat/harm (NNT/NNH) were calculated to derive the Likelihood of being Helped or Harmed (LHH). Data from 15 trials (3601 patients) were included. Paclitaxel significantly increases pCR rate by 6.8% in comparison with docetaxel (43.4%, 95% CI 41.1-45.7% versus 36.6%, 95% CI 34.3-39.0%, p=0.0001), regardless of the chemotherapy backbone, with an absolute difference of 9% and 9.2% for anthracycline-based or free-regimens. Paclitaxel significantly improves pCR versus docetaxel with a single HER2-inhibition by 6.7% (p=0.0012), with no difference if combined with a dual HER2-inhibition. Severe neutropenia and FN are significantly lower with paclitaxel, with an absolute difference of 32.4% (p<0.0001) and 2.5% (p=0.0059), respectively. Conversely, severe neurotoxicity is slightly higher with paclitaxel (3%, p=0.0001). The LHH ratio calculated for pCR and severe neutropenia is 2.0 and 0.7 for paclitaxel and docetaxel. Although the activity of neoadjuvant paclitaxel and docetaxel HER2-positive breast cancer is considered similar, the slight advantage in pCR, the significantly lower neutropenia and FN, do favor paclitaxel (in the weekly fashion) over docetaxel, despite the slightly worst neurotoxicity.
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. Electronic address: luisa.carbognin@gmail.com.
authors: Luisa
authors: L
authors: Carbognin
authors: Biostatistics, Regina Elena National Cancer Institute, Roma, Italy. Electronic address: isperduti@yahoo.it.
authors: Isabella
authors: I
authors: Sperduti
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. Electronic address: rolando.nortilli@ospedaleuniverona.it.
authors: Rolando
authors: R
authors: Nortilli
authors: Department of Pathology and Diagnostic, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. Electronic address: matteo.brunelli@univr.it.
authors: Matteo
authors: M
authors: Brunelli
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. Electronic address: cecivice@gmail.com.
authors: Cecilia
authors: C
authors: Vicentini
authors: Chirurgia 'A', Department of Surgery and Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. Electronic address: francesca.pellini@ospedaleuniverona.it.
authors: Francesca
authors: F
authors: Pellini
authors: Chirurgia 'A', Department of Surgery and Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. Electronic address: giovanni.pollini@ospedaleuniverona.it.
authors: Giovanni Paolo
authors: GP
authors: Pollini
authors: Biostatistics, Regina Elena National Cancer Institute, Roma, Italy. Electronic address: giannarelli@ifo.it.
authors: Diana
authors: D
authors: Giannarelli
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. Electronic address: giampaolo.tortora@univr.it.
authors: Giampaolo
authors: G
authors: Tortora
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. Electronic address: emilio.bria@univr.it.
authors: Emilio
authors: E
authors: Bria
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D000077143:Docetaxel; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000077143:Docetaxel; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C508053:ERBB2 protein, human
keywords: Breast cancer; Docetaxel; HER2-positive; Neoadjuvant; Paclitaxel; Sensitivity analysis