Breast Cancer Research (2020-08-01)

EFFECT: a randomized phase II study of efficacy and impact on function of two doses of nab-paclitaxel as first-line treatment in older women with advanced breast cancer

  • Laura Biganzoli,
  • Saverio Cinieri,
  • Rossana Berardi,
  • Rebecca Pedersini,
  • Amelia McCartney,
  • Alessandro Marco Minisini,
  • Elena Rota Caremoli,
  • Simon Spazzapan,
  • Emanuela Magnolfi,
  • Antonella Brunello,
  • Emanuela Risi,
  • Raffaella Palumbo,
  • Silvana Leo,
  • Marco Colleoni,
  • Sara Donati,
  • Sabino De Placido,
  • Laura Orlando,
  • Mirco Pistelli,
  • Veronica Parolin,
  • Anna Mislang,
  • Dimitri Becheri,
  • Fabio Puglisi,
  • Giuseppina Sanna,
  • Elena Zafarana,
  • Luca Boni,
  • Giuseppe Mottino

Journal volume & issue
Vol. 22, no. 1
pp. 1 – 11


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Abstract Background Limited data are available regarding the use of nab-paclitaxel in older patients with breast cancer. A weekly schedule is recommended, but there is a paucity of evidence regarding the optimal dose. We evaluated the efficacy of two different doses of weekly nab-paclitaxel, with a specific focus on their corresponding impact on patient function, in order to address the lack of data specifically relating to the older population. Methods EFFECT is an open-label, phase II trial wherein 160 women with advanced breast cancer aged ≥ 65 years were enrolled from 15 institutions within Italy. Patients were randomly assigned 1:1 to receive nab-paclitaxel 100 mg/m2 (arm A) or 125 mg/m2 (arm B) on days 1, 8, and 15 on a 28-day cycle, as first-line treatment for advanced disease. The primary endpoint was event-free survival (EFS), wherein an event was defined as disease progression (PD), functional decline (FD), or death. In each arm, the null hypothesis that the median EFS would be ≤ 7 months was tested against a one-sided alternative according to the Brookmeyer Crowley test. Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. Results After a median follow-up of 32.6 months, 140 events were observed in 158 evaluable patients. Median EFS was 8.2 months (90% CI, 5.9–8.9; p = 0.188) in arm A vs 8.3 months (90% CI, 6.2–9.7, p = 0.078) in arm B. Progression-free survival, overall survival, and response rates were similar in both groups. A higher percentage of dose reductions and discontinuations due to adverse events (AEs) was noted in arm B. The most frequently reported non-haematological AEs were fatigue (grade [G] 2–3 toxicity occurrence in arm A vs B, 43% and 51%, respectively) and peripheral neuropathy (G2–3 arm A vs B, 19% and 38%, respectively). Conclusion Pre-specified outcomes were similar in both treatment arms. However, 100 mg/m2 was significantly better tolerated with fewer neurotoxicity-related events, representing a more feasible dose to be recommended for older patients with advanced disease. Trial registration EudraCT, 2012-002707-18 . Registered on June 4, 2012. NIH, NCT02783222 . Retrospectively registered on May 26, 2016.