A phase 3 safety study of fosnetupitant as an antiemetic in patients receiving anthracycline and cyclophosphamide: CONSOLE-BC.


Journal

Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236

Informations de publication

Date de publication:
15 04 2022
Historique:
revised: 10 12 2021
received: 21 10 2021
accepted: 13 12 2021
pubmed: 20 1 2022
medline: 7 4 2022
entrez: 19 1 2022
Statut: ppublish

Résumé

Fosnetupitant (FosNTP), an intravenous neurokinin 1 receptor antagonist, demonstrated a favorable safety profile with a potentially low risk of injection site reactions (ISRs) and promising antiemetic efficacy in patients receiving cisplatin-based highly emetogenic chemotherapy in a previous phase 2 study. We conducted a randomized, double-blind safety study to evaluate the safety profile of FosNTP, including ISRs, in patients receiving doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide (AC/EC) chemotherapy. Patients scheduled to receive AC/EC were randomized 1:1 to receive 235 mg of FosNTP or 150 mg of fosaprepitant (FosAPR), both in combination with 0.75 mg of intravenous palonosetron and 9.9 mg of dexamethasone on day 1. The stratification factors were age category (<55 vs ≥55 years) and study site. The primary end point was the incidence of treatment-related adverse events (TRAEs) with FosNTP. Overall, 102 patients were randomized to FosNTP (n = 52) or FosAPR (n = 50), and all were treated with the study drug and evaluated for safety. The primary end point, the incidence of TRAEs, was similar with FosNTP (21.2%; 95% confidence interval [CI], 11.1%-34.7%) and FosAPR (22.0%; 95% CI, 11.5%-36.0%), with any-cause ISRs observed in 5.8% and 26.0% of patients, respectively, and treatment-related ISRs observed in 0% and 10.0%, respectively. The overall (0-120 hour) complete response (defined as no emetic event and no rescue medication) rate, standardized by age category in the full analysis set, was 45.9% (23 of 51 patients) with FosNTP and 51.3% (25 of 49 patients) with FosAPR. FosNTP demonstrated a favorable safety profile with a very low risk of ISRs in the AC/EC setting.

Sections du résumé

BACKGROUND
Fosnetupitant (FosNTP), an intravenous neurokinin 1 receptor antagonist, demonstrated a favorable safety profile with a potentially low risk of injection site reactions (ISRs) and promising antiemetic efficacy in patients receiving cisplatin-based highly emetogenic chemotherapy in a previous phase 2 study. We conducted a randomized, double-blind safety study to evaluate the safety profile of FosNTP, including ISRs, in patients receiving doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide (AC/EC) chemotherapy.
METHODS
Patients scheduled to receive AC/EC were randomized 1:1 to receive 235 mg of FosNTP or 150 mg of fosaprepitant (FosAPR), both in combination with 0.75 mg of intravenous palonosetron and 9.9 mg of dexamethasone on day 1. The stratification factors were age category (<55 vs ≥55 years) and study site. The primary end point was the incidence of treatment-related adverse events (TRAEs) with FosNTP.
RESULTS
Overall, 102 patients were randomized to FosNTP (n = 52) or FosAPR (n = 50), and all were treated with the study drug and evaluated for safety. The primary end point, the incidence of TRAEs, was similar with FosNTP (21.2%; 95% confidence interval [CI], 11.1%-34.7%) and FosAPR (22.0%; 95% CI, 11.5%-36.0%), with any-cause ISRs observed in 5.8% and 26.0% of patients, respectively, and treatment-related ISRs observed in 0% and 10.0%, respectively. The overall (0-120 hour) complete response (defined as no emetic event and no rescue medication) rate, standardized by age category in the full analysis set, was 45.9% (23 of 51 patients) with FosNTP and 51.3% (25 of 49 patients) with FosAPR.
CONCLUSIONS
FosNTP demonstrated a favorable safety profile with a very low risk of ISRs in the AC/EC setting.

Identifiants

pubmed: 35045185
doi: 10.1002/cncr.34088
pmc: PMC9306508
doi:

Substances chimiques

Anthracyclines 0
Antiemetics 0
Dexamethasone 7S5I7G3JQL
Cyclophosphamide 8N3DW7272P

Banques de données

JapicCTI
['JapicCTI-194691']

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1692-1698

Subventions

Organisme : Taiho Pharmaceutical

Informations de copyright

© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.

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Auteurs

Kazuo Matsuura (K)

Department of Breast Oncology, Saitama Medical University International Medical Center, Saitama, Japan.

Junji Tsurutani (J)

Advanced Cancer Translational Research Institute, Showa University, Tokyo, Japan.

Kenichi Inoue (K)

Department of Breast Oncology, Saitama Cancer Center, Saitama, Japan.

Yuko Tanabe (Y)

Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan.

Tetsuhiko Taira (T)

Department of Medical Oncology, Sagara Hospital, Kagoshima, Japan.

Kaoru Kubota (K)

Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.

Tomohide Tamura (T)

Thoracic Center, St. Luke's International Hospital, Tokyo, Japan.

Toshiaki Saeki (T)

Department of Breast Oncology, Saitama Medical University International Medical Center, Saitama, Japan.

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Classifications MeSH