LBA97 - Olanzapine for the prevention of chemotherapy induced nausea vomiting in patients receiving moderately emetogenic chemotherapeutic (MEC) regimens: Results of a prospective triple blinded phase III multicentric study (OMEC)

Background

MEC regimens have lesser than expected control of nausea and vomiting with standard antiemetic prophylaxis. The role of olanzapine has not been adequately evaluated with these regimens.

Methods

In this randomized multicentric, triple-blind, phase 3 trial, we compared dexamethasone, aprepitant and palonosetron without (standard) or with the addition of olanzapine (experimental) in patients who were receiving oxaliplatin, carboplatin or irinotecan-based chemotherapy (MEC). The experimental group received 10 mg of olanzapine orally once at night on days 1 through 3. Complete response, defined as the proportion of subjects with no vomiting and no significant nausea, scored as < 5 on a visual analogue scale of 1-100, was the primary endpoint. The quality of life (QOL) was assessed by the Functional Living Index Emesis (FLIE). The study required to recruit 560 patients (280 patients per arm) to show preplanned improvement in CR rates.

Results

Of the 544 evaluable patients, baseline characteristics were evenly matched between the two groups. The proportion of patients with CR was significantly greater with olanzapine than without olanzapine in the overall 120-hour period (92.3% vs. 86.2%, P=0.022). The proportion of patients with no chemotherapy-induced nausea as well as combined chemotherapy induced nausea and vomiting (CINV) were significantly more with olanzapine than without in the period from 25 to 120 hours (delayed CINV) (nausea 96.7% vs. 88.5% p<0.001; CINV 95.3% vs. 86.3%; p<0.001). The overall use of rescue medications was lesser in patients receiving olanzapine (4% vs. 11.5%p=0.001). The use of olanzapine at 10 mg per day was not associated with any significant toxicities and QOL did not deteriorate by the addition of the olanzapine as assessed by FLIE.

Conclusions

The addition of olanzapine significantly improved CR rates as well as delayed CINV rates in previously untreated patients who were receiving moderately emetogenic chemotherapeutic regimens containing oxaliplatin, carboplatin or irinotecan. The use of olanzapine should be considered as standard of care in these chemotherapeutic regimens.

Clinical trial identification

CTRI/2018/12/016643.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Cadilla Pharma PVT Ltd Dr Reddy's Lab PVT Ltd.

Disclosure

V.S. Ostwal: Financial Interests, Institutional, Advisory Board: Panacea, Reddy's Lab pvt limited, AstraZeneca, Zydus Cadila; Financial Interests, Personal, Invited Speaker, Expenses for travel and accommodation: AstraZeneca; Financial Interests, Institutional, Funding, Educational Grant: Reddy's Lab, Zydus Cadila; Financial Interests, Institutional, Other, Drug support: Intas Pharma pvt ltd, Esai Pharma, Alkem pvt ltd; Financial Interests, Institutional, Other, drug support: Micro Labs private limited; Non-Financial Interests, Leadership Role, secretary of Supportive care organization in India: Indian Association of supportive care in Cancer. A. Ramaswamy: Financial Interests, Institutional, Research Grant: Cipla Health Limited, Dr Reddy Laboratories, Zydus Lifesciences. P.G. Bhargava: Financial Interests, Institutional, Invited Speaker: Novartis, Intas, Roche, Pfizer; Financial Interests, Institutional, Advisory Board: Mankind, Zydus. I.N. Olver: Financial Interests, Personal, Invited Speaker, Subsidised airfare and accomodation to speak at the 2022 Annual Scientific Mettign In Toronto in June 2022: Multinational Association of Supportive Care in Cancer; Financial Interests, Personal, Advisory Board, On advisory board for this digital and oncology management platform company: Viecure; Financial Interests, Personal, Advisory Board, Provide advice on development of cannabinoids: BOD; Financial Interests, Personal, Full or part-time Employment, Pratt time employee as a professorial research fellow in the School of Psychology: University of Adelaide; Financial Interests, Personal, Full or part-time Employment, Employed by the Department of Medicine to teach ethics: University of Notre Dame Australia; Financial Interests, Personal, Full or part-time Employment, Sit on Bellberry Ethics Committees: Bellberry Ltd; Non-Financial Interests, Member of Board of Directors, Chair the Board of this knowledge generation institute: Sax Insittute; Non-Financial Interests, Member of Board of Directors, Sit on the Board of this charity that focuses on screening and prevention of bowel cancer: Jodie Lee Foundation. All other authors have declared no conflicts of interest.