TY - JOUR
T1 - 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
T2 - A collaboration with the European Innovative Therapies for Children with Cancer Network
AU - Amoroso, Loredana
AU - Castel, Victoria
AU - Bisogno, Gianni
AU - Casanova, Michela
AU - Marquez-Vega, Catalina
AU - Chisholm, Julia C.
AU - Doz, François
AU - Moreno, Lucas
AU - Ruggiero, Antonio
AU - Gerber, Nicolas U.
AU - Fagioli, Franca
AU - Hingorani, Pooja
AU - Melcón, Soledad G.
AU - Slepetis, Ruta
AU - Chen, Nianhang
AU - le Bruchec, Yvan
AU - Simcock, Mathew
AU - Vassal, Gilles
N1 - Funding Information:
The authors thank all the patients and their families, as well as the medical teams at the centers for their participation in the trial. The authors also thank Yan Li for conducting pharmacokinetic experiments for the study. Writing assistance was provided by Rebecca Tweedell, PhD, of MediTech Media, Ltd, through funding by Bristol-Myers Squibb Company . The authors are fully responsible for all content and editorial decisions for this manuscript. J.C.C. is supported by National Health Service funding to the National Institute for Health Research Biomedical Research Centre of the Royal Marsden Hospital. L.M. was supported by a Juan Rodés Research Fellowship of Instituto de Salud Carlos III (Instituto de Investigación Sanitaria La Princesa).
Funding Information:
This work was supported by Bristol-Myers Squibb Company, Princeton, NJ.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 interestThe authors thank all the patients and their families, as well as the medical teams at the centers for their participation in the trial. The authors also thank Yan Li for conducting pharmacokinetic experiments for the study. Writing assistance was provided by Rebecca Tweedell, PhD, of MediTech Media, Ltd, through funding by Bristol-Myers Squibb Company. The authors are fully responsible for all content and editorial decisions for this manuscript. J.C.C. is supported by National Health Service funding to the National Institute for Health Research Biomedical Research Centre of the Royal Marsden Hospital. L.M. was supported by a Juan Rod?s Research Fellowship of Instituto de Salud Carlos III (Instituto de Investigaci?n Sanitaria La Princesa).
Funding Information:
This work was supported by Bristol-Myers Squibb Company, Princeton, NJ .
Publisher Copyright:
© 2020
PY - 2020/8
Y1 - 2020/8
N2 - 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/m2 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.
AB - 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/m2 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.
KW - Albumin-bound paclitaxel
KW - Ewing sarcoma
KW - Neuroblastoma
KW - Paediatric
KW - Rhabdomyosarcoma
KW - Solid tumour
UR - http://www.scopus.com/inward/record.url?scp=85086371362&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086371362&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2020.04.031
DO - 10.1016/j.ejca.2020.04.031
M3 - Article
C2 - 32554315
AN - SCOPUS:85086371362
SN - 0959-8049
VL - 135
SP - 89
EP - 97
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -