Antonella Brunello, Silvana Leo, Emanuela Magnolfi, Sabino De Placido, Raffaella Palumbo, Alessandro Marco Minisini, Elena Rota Caremoli, Elena Zafarana, Sara Donati, Emanuela Risi, Anna Rachelle Mislang, Giuseppe Mottino, Luca Boni, Dimitri Becheri, Rossana Berardi, Mirco Pistelli, Fabio Puglisi, Amelia McCartney, Rebecca Pedersini, Laura Biganzoli, Veronica Parolin, Simon Spazzapan, Giuseppina Sanna, Saverio Cinieri, Marco Colleoni, Laura Orlando, Biganzoli, Laura, Cinieri, Saverio, Berardi, Rossana, Pedersini, Rebecca, Mccartney, Amelia, Minisini, Alessandro Marco, Caremoli, Elena Rota, Spazzapan, Simon, Magnolfi, Emanuela, Brunello, Antonella, Risi, Emanuela, Palumbo, Raffaella, Leo, Silvana, Colleoni, Marco, Donati, Sara, De Placido, Sabino, Orlando, Laura, Pistelli, Mirco, Parolin, Veronica, Mislang, Anna, Becheri, Dimitri, Puglisi, Fabio, Sanna, Giuseppina, Zafarana, Elena, Boni, Luca, and Mottino, Giuseppe
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 ClinicalTrials.gov, NCT02783222. Retrospectively registered on May 26, 2016.