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 1,8,15 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, versus 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-hematological AEs were fatigue (grade [G] 2-3 toxicity occurrence in Arm A versus B: 43% and 51%, respectively) and peripheral neuropathy (G2-3 Arm A versus 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.
EudraCT identifier: 2012-002707-18, registered June 4 2012 - https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-002707-18/IT#E . NIH ClinicalTrials.gov identifier: NCT02783222, registered May 26 2016 – retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02783222