NE Oncology Issue – June 2007

New data show improved clinical activity of nab-paclitaxel compared with docetaxel in patients with advanced breast cancer

Background

The first generation taxanes, paclitaxel and docetaxel, have provided major improvements in the treatment of early-stage and metastatic breast cancer, but contain required chemical solvents that are associated with toxicity. Response rates of 40% to 60% have been reported in chemotherapy-naïve patients with metastatic breast cancer treated with paclitaxel, and rates of 25% to 30% in patients refractory to anthracycline-containing regimens.1 Current studies are assessing whether nab-paclitaxel can offer the same antitumour effect as docetaxel, as a previous phase III trial has already demonstrated superiority of nab-paclitaxel over paclitaxel in MBC, in addition to its advantages, which include lack of premedication and shorter infusion time.2,3 A poster presented by William Gradishar and colleagues referred to data from the fourth interim analysis of a randomized, open-label phase II study of weekly or every-three-week nab-paclitaxel compared to docetaxel every three weeks as first-line therapy in patients with metastatic breast cancer.4

Study design

  • This current four-arm trial compares toxicity and preliminary efficacy data for
    • solvent-free nab-paclitaxel versus solvent-based docetaxel
    • nab-paclitaxel every week versus every three weeks (Q3W)
    • high-dose versus low-dose weekly (QW) nab-paclitaxel
  • Patients had no prior chemotherapy for metastatic disease, Stage IV adenocarcinoma of the breast, and adequate liver function.
  • Three hundred patients were enrolled who had a mean age of 54 years, and 75% were postmenopausal.
  • Primary outcomes were antitumour response (evaluated every eight weeks by RECIST criteria) and toxicity.
  • The secondary outcome measure was progression-free survival (PFS).
  • The investigator-confirmed response assessments were compared with secondary response assessments conducted by an independent radiology review.
  • The independent radiology reviewer was blinded to treatment assignment, investigator assessment of response, and target lesions identified by investigator.

asco07-1-study-lrg

Key findings

  • The nab-paclitaxel Q3W regimen significantly improved progression-free survival compared with docetaxel Q3W (Figure 1).
    • nab-paclitaxel 300 mg/m2 Q3W versus docetaxel, HR = 0.63, p = 0.046
  • The nab-paclitaxel QW high-dose regimen significantly improved progression-free survival compared with docetaxel Q3W.
    • nab-paclitaxel 150 mg/m2 QW versus docetaxel, HR = 0.46, p = 0.002
    • nab-paclitaxel 100 mg/m2 QW versus docetaxel, HR = not significant
    • The higher dose of weekly nab-paclitaxel (150 mg/m2 QW) was significantly better than the lower weekly dose (100 mg/m2); HR = 0.55, p = 0.009.
  • Nab-paclitaxel QW (100 and 150 mg/m2) significantly increased tumour response rate compared with docetaxel given every three weeks (Figure 2).
    • nab-paclitaxel 100 mg/m2 QW versus docetaxel 100 mg/m2 Q3W (p = 0.002)
    • nab-paclitaxel 150 mg/m2 QW versus docetaxel 100 mg/m2 Q3W (p = 0.003)

Safety

  • The low-dose weekly arm appeared to be the most tolerable of the three nab-paclitaxel arms.
    • All the nab-paclitaxel arms had significantly less neutropenia than the docetaxel arm. Neutropenia (all grades) was significantly more common in the every-three-weeks arm and high-dose weekly arm of nab-paclitaxel compared with the low-dose weekly arm (Tables 1 and 2).
  • The rate of febrile neutropenia was lower in all nab-paclitaxel arms compared with docetaxel.
  • There was also a lower incidence of fatigue with all schedules of nab-paclitaxel compared with docetaxel.
  • No difference was observed in peripheral neuropathy rates between nab-paclitaxel arms and docetaxel.
    • The 100 mg/m2 arm of nab-paclitaxel was associated with the least peripheral neuropathy.
  • Grade 1 and 2 arthralgias were significantly more common in the every-three-weeks arm and the high-dose weekly arm of nab-paclitaxel compared with the low-dose weekly arm.
  • However, grade 1 and 2 arthralgias were more common in the every-three-week arm (p = 0.021) and high-dose (150 mg/m2) weekly (p = 0.048) nab-paclitaxel arms compared with docetaxel.

Key conclusions

  • The response rate was observed to be superior for both the 100 mg/m2 and 150 mg/m2 weekly doses of nab-paclitaxel compared with docetaxel in metastatic breast cancer.
  • Progression-free survival was significantly improved with weekly nab-paclitaxel 150 mg/m2 and nab-paclitaxel 300 mg/m2 every three weeks compared with docetaxel.
  • Progression-free survival was superior for the weekly nab-paclitaxel 150 mg/m2 compared with weekly nab-paclitaxel 100 mg/m2.
  • Adverse events such as neutropenia and fatigue were fewer with all schedules of nab-paclitaxel compared with docetaxel.
  • A large randomized phase III trial comparing weekly (three weeks out of four) nab-paclitaxel 150 mg/m2 versus Q3W docetaxel 100 mg/m2 (every three weeks) in metastatic breast cancer is to begin shortly.

References: 1. Nabholtz JM, Tonkin K, Smylie M, et al. Chemotherapy of breast cancer: are the taxanes going to change the natural history of breast cancer? Expert Opin Pharmacother 2000;1:187–206. 2. Gradishar WJ, Tjulandin S, Davidson N, et al. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol 2005;23:7794–7803. 3. Jones SE, Erban J, Overmoyer B, et al. Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol. 2005;23:5542–5551. 4. Gradishar W, Krasnojon D, Cheporov S, et al. Randomized comparison of weekly or every-3-week (q3w) nab-paclitaxel compared to q3w docetaxel as first-line therapy in patients (pts) with metastatic breast cancer (MBC). Program and abstracts of the 43rd American Society of Clinical Oncology Annual Meeting; June 1–5, 2007; Chicago, Illinois; Abstract 1032.