Abstract 1728
Background
Olanzapine (OLZ) 10 mg added to standard antiemetic therapy including aprepitant (APR), palonosetron (PALO), and dexamethasone (DEX) has been recommended for the prevention of chemotherapy-induced nausea and vomiting (CINV) caused by cisplatin. Guidelines suggest that OLZ at a dose of 5 mg should be taken into consideration in patients at risk of sedation. OLZ 5 mg showed an equivalent activity and favorable toxicity to somnolence in several phase II studies. We conducted a randomized, double-blind, placebo-controlled phase III trial to evaluate OLZ 5 mg in addition to standard antiemetic therapy for the prevention of CINV.
Methods
Patients receiving cisplatin (≥ 50 mg/m2) were randomly assigned to either OLZ 5 mg or placebo on days 1–4, combined with APR, PALO and DEX. The primary endpoint was complete response (CR), defined as no vomiting and no rescue medications in the delayed phase (24–120 h). As the secondary endpoints, frequency of sleepiness during daytime and appetite loss were assessed by patient reported outcome.
Results
A total of 710 patients were enrolled (OLZ 356 and placebo 354). CR in the delayed phase was significantly increased with OLZ than with placebo (79% vs. 66%, P < 0.001). CR in the acute (0–24 h) and overall (0–120 h) phase was also significantly increased with OLZ (95% vs. 89%, P = 0.002, and 78% vs. 64%, P < 0.001, respectively). Although the proportion of sleepiness during daytime was higher in the OLZ group than the placebo group on day 1 (75% vs. 68%, P = 0.002), there was no difference found on days 2–5 between the two groups. The proportion of patients who reported appetite loss was significantly lower in the OLZ group than the placebo group on days 2–5 (P < 0.001).
Conclusions
OLZ 5 mg can be considered a new standard antiemetic therapy in patients receiving cisplatin-based chemotherapy. Sleepiness during daytime due to OLZ 5 mg seems to be tolerable and addition of OLZ 5mg to the standard antiemetic therapy may reduce appetite loss.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Masakazu Abe.
Funding
Japan Agency for Medical Research and Development.
Disclosure
S. Iwasa: Honoraria (self): Taiho pharmaceutical; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self): Ono Pharmaceutical; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Bristol-Myers Squib; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Otsuka; Research grant / Funding (institution): Bayer. N. Yamamoto: Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Research grant / Funding (institution): Taiho Pharmaceutical; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Kyowa Hakko Kirin; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): IQVIA; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Merck Serono. Y. Ohe: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly Japan; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options, An Immediate Family Member : Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Kyorin; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy: Celltrion; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bayer; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (institution): Taiho pharmaceutical; Honoraria (self): Kyowa Hakko Kirin; Research grant / Funding (institution): Sumitomo Dainippon Pharma; Research grant / Funding (institution): Ignyta. All other authors have declared no conflicts of interest.
Resources from the same session
3158 - Tobacco Retail Access and Tobacco Cessation Among Head and Neck Cancer (HNC) Survivors
Presenter: Lawson Eng
Session: Poster Display session 1
Resources:
Abstract
5511 - ASSERT: A Prospective, Observational Study Measuring Sodium Improvement and Outcomes in Patients Treated for Moderate to Severe Hyponatremia Secondary to Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) in Italy (Lung Cancer Cohort)
Presenter: Rossana Berardi
Session: Poster Display session 1
Resources:
Abstract
3821 - Efficacy and safety of controlled ovarian stimulation with or without letrozole co-administration for fertility preservation: A systematic review and meta-analysis.
Presenter: Benedetta Bonardi
Session: Poster Display session 1
Resources:
Abstract
2168 - Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy
Presenter: Tineke Vandenbroucke
Session: Poster Display session 1
Resources:
Abstract
5855 - Update of the registry of young women with cancer by the International Network of Cancer, Infertility and Pregnancy
Presenter: Charlotte Maggen
Session: Poster Display session 1
Resources:
Abstract
5156 - Erectile dysfunction in patients with metastatic renal cell carcinoma
Presenter: Ilya Tsimafeyeu
Session: Poster Display session 1
Resources:
Abstract
4992 - Exercise level, interest and preferences in cancer patients.
Presenter: Alice Avancini
Session: Poster Display session 1
Resources:
Abstract
3427 - Filling the Gaps in Informed Consent for Advanced Cancer Patients considering Phase 1 Oncology Trials - an in-depth Qualitative Study of Key Stakeholders at a large United Kingdom Phase 1 unit
Presenter: Abhijit Pal
Session: Poster Display session 1
Resources:
Abstract
3537 - Breast Cancer Patients’ Quality of Life: Real World Data
Presenter: Thanos Kosmidis
Session: Poster Display session 1
Resources:
Abstract
4761 - High-sensitivity troponin as a cardiotoxicity biomarker in breast cancer treatment
Presenter: Joana Simões
Session: Poster Display session 1
Resources:
Abstract