Phase II results from a phase I/II study to assess the safety and efficacy of weekly nab-paclitaxel in paediatric patients with recurrent or refractory solid tumours: A collaboration with the European Innovative Therapies for Children with Cancer Network.

Background: The phase I component of a phase I/II study defined the recommended phase II dose and established the tolerability of nab-paclitaxel monotherapy in paediatric patients with recurrent or refractory solid tumours. The activity and safety of nab-paclitaxel monotherapy was further investigated in this phase II study.
Patients and Methods: Paediatric patients with recurrent or refractory Ewing sarcoma, neuroblastoma or rhabdomyosarcoma received 240 mg/m ² of nab-paclitaxel on days 1, 8 and 15 of each 28-day cycle. The primary end-point was the overall response rate (ORR; complete response [CR] + partial response [PR]). Secondary end-points included duration of response, disease control rate (DCR; CR + PR + stable disease [SD]), progression-free survival, 1-year overall survival, safety and pharmacokinetics.
Results: Forty-two patients were enrolled, 14 each with Ewing sarcoma, neuroblastoma and rhabdomyosarcoma. The ORRs were 0%, 0% and 7.1% (1 confirmed PR), respectively. The DCRs were 30.8% (4 SD), 7.1% (1 SD) and 7.1% (1 confirmed PR and 0 SD) in the Ewing sarcoma, neuroblastoma and rhabdomyosarcoma groups, respectively. The median progression-free survival was 13.0, 7.4 and 5.1 weeks, respectively, and the 1-year overall survival rates were 48%, 25% and 15%, respectively. The most common grade III/4IVadverse events were haematologic (neutropenia [50%] and anaemia [48%]), and grade III/IV peripheral neuropathy occurred in 2 patients (14%) in the rhabdomyosarcoma group. Pharmacokinetics analyses revealed that paclitaxel tissue distribution was both rapid and extensive.
Conclusions: In this phase II study, limited activity was observed; however, the safety of nab-paclitaxel in paediatric patients was confirmed.
Trial Registration: NCT01962103 and EudraCT 2013-000144-26.
Competing Interests: Conflict of interest statement G.B. reports serving in a consulting or advisory role for Clinigen Group and receiving travel expenses from Jazz Pharmaceuticals. J.C.C. reports serving in a consulting or advisory role for Bayer and Roche. F.D. reports serving in a consulting or advisory role for Bristol-Myers Squibb and Celgene (a Bristol-Myers Squibb Company), from which his institution has received funds, and receiving travel expenses from Bristol-Myers Squibb. L.M. reports serving in a consulting or advisory role for Novartis, AstraZeneca, Roche Genentech, Bayer, Amgen and MundiPharma; receiving honoraria for educational events from Celgene (a Bristol-Myers Squibb Company) and Novartis and receiving travel expenses from MundiPharma, Celgene (a Bristol-Myers Squibb Company) and Amgen. S.G.M. reports being in a paid advisory role for Loxo Oncology and Clinigen Group for work performed outside of the current study. R.S. reports serving as an employee of and holding stock/ownership in Bristol-Myers Squibb. N.C. reports serving as an employee of and holding stock/ownership in Bristol-Myers Squibb. Y.l.-B. reports serving as an employee of Celgene (a Bristol-Myers Squibb Company) International A Bristol-Myers Squibb Company and holding stock/ownership in Bristol-Myers Squibb. M.S. reports serving as an employee of Celgene (a Bristol-Myers Squibb Company) International A Bristol-Myers Squibb Company and holding stock/ownership in Bristol-Myers Squibb. G.V. reports receiving travel expenses from Bristol-Myers Squibb. All other authors declare no conflict of interest
(Published by Elsevier Ltd.)