Abstract 455P
Background
The anticancer treatment landscape is rapidly evolving with the introduction of novel targeted therapies. Nausea and vomiting (NV) are expected with anticancer treatment and these adverse events have been reported post-treatment for up to 120 h (5 days). However, introduction of new treatments with a different mechanism of action may require post-treatment NV monitoring for longer than the overall phase (traditionally defined as 0 h to 120 h). Emerging data following antibody-drug conjugates (ADCs) treatment suggests NV can occur for a longer time, potentially resulting in detrimental effects on quality of life and poor adherence to targeted treatment. Netupitant, a highly selective NK1 receptor antagonist used for NV prevention, has recently demonstrated favorable comparative efficacy to aprepitant during an extended overall phase (assessed up to 168 h), likely due in part to its long half-life. We conducted an analysis aimed at evaluating netupitant striatum RO for an extended time interval.
Methods
Data from previous pharmacokinetic (PK) studies in a Caucasian population were described by PK models and the rate, extent, and duration of NK1 RO with netupitant were predicted by pharmacodynamic modeling in their respective relevant tissues (Baron-Hay, Supp Care Cancer 2019). This model was applied in this analysis to determine the netupitant NK1 RO percent in the striatum region up to 240 h.
Results
Netupitant NK1 RO was predicted to reach 90% at 2.2 h after drug administration. RO began to decline slowly after 24 h, reaching 70% at 168 h (Day 7) and remained above 59% through 240 h (Day 10). Table: 455P
Model-predicted striatum NK1 RO as a function of time after netupitant 300 mg administration
Time (hour) | RO (percent) |
3 | 91.2 |
6 | 91.4 |
12 | 90.8 |
24 | 88.9 |
48 | 84.2 |
72 | 80.7 |
96 | 78.1 |
120 | 75.6 |
144 | 72.9 |
168 | 70.0 |
192 | 66.8 |
216 | 63.3 |
240 | 59.6 |
Conclusions
Netupitant has the potential to protect patients from NV for an extended time period, perhaps due to its long half-life and persistent NK1 RO, making it a promising antiemetic for prevention of NV with new anticancer targeted therapy including ADCs.
Clinical trial identification
Editorial acknowledgement
Editorial and medical writing assistance was provided by Jennifer Vanden Burgt, an independent Medical Affairs consultant, Minneapolis, MN and funded by Helsinn Healthcare SA, Lugano, Switzerland.
Legal entity responsible for the study
Helsinn Healthcare.
Funding
Helsinn Healthcare.
Disclosure
F. Scotté: Financial Interests, Personal, Advisory Board, Meetings: Leo Pharma; Financial Interests, Personal, Invited Speaker, symposia: Amgen, MSD, Thermofisher, BMS, Pfizer, MundiPharma, Tilray; Financial Interests, Personal, Invited Speaker: Pierre Fabre Oncology, Clovis Oncology; Financial Interests, Personal, Advisory Board: Viatris-Mylan, Viforpharma, Helsinn, Chugai, Sanofi, Sandoz, GSK; Non-Financial Interests, Personal, Other, member of faculty for supportive and palliative care: ESMO; Non-Financial Interests, Personal, Member of Board of Directors: MASCC, AFSOS. L. Zelek: Financial Interests, Personal, Advisory Board: Vifor, Novartis, Roche, Eli Lilly, Sandoz, Pfizer. C. Giuliano, S. Olivari Tilola: Financial Interests, Personal, Full or part-time Employment: Helsinn Healthcare . W.L. Bailey: Financial Interests, Personal, Full or part-time Employment: Helsinn Therapeutics. C.H. Ruhlmann: Financial Interests, Institutional, Coordinating PI, Funding for a clinical trial.: Helsinn Healthcare. H. Iihara: Financial Interests, Institutional, Advisory Board: Taiho Pharmaceutical Co., Ltd., Eisai Co., Ltd.; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., AstraZeneca plc, Nippon Kayaku Co., Ltd., Ono Pharmaceutical Co., Ltd., Eli Lilly and Company, Nippon Boehringer Ingelheim Co., Ltd.; Financial Interests, Personal, Other, Invited Speaker and Workshop Facilitator: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Other, Interviewing and Supervision: Astellas Pharma Co., Ltd.; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical Co., Ltd., Asahi Kasei Pharma Co., Ltd., Mochida Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Japan Blood Products Organization, Nippon Kayaku Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Nippon Kayaku Co., Ltd. M.S. Aapro: Financial Interests, Personal, Invited Speaker: Amgen, ViforPharma; Financial Interests, Institutional, Other, Grant to SPCC: BMS, ExactSciences, Pfizer, Novartis, Roche, AstraZeneca; Financial Interests, Institutional, Invited Speaker, Grant to SPCC: Helsinn; Financial Interests, Institutional, Other, GRANT TO SPCC: Mundipharma, Fresenius Kabi, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Member of Board of Directors: European Cancer Organisation, SIOG, UICC; Financial Interests, Institutional, Member of Board of Directors: SPCC, ALL CAN; Non-Financial Interests, Personal, Advisory Role, Confidentiality agreement: Various companies; Non-Financial Interests, Personal, Leadership Role: European Cancer Organisation, SPCC, SIOG; Non-Financial Interests, Personal, Member: MASCC, SBOC, ASCO; Other, Personal, Other, SAB member: European School of Oncology.
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