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Clinical Trial
. 2024 Aug 1;7(8):e2426076.
doi: 10.1001/jamanetworkopen.2024.26076.

Olanzapine as Antiemetic Prophylaxis in Moderately Emetogenic Chemotherapy: A Phase 3 Randomized Clinical Trial

Vikas Ostwal  1 , Anant Ramaswamy  1 , Sarika Mandavkar  1 , Prabhat Bhargava  1 , Deepali Naughane  1 , Sharon Flavia Sunn  1 , Sujay Srinivas  1 , Akhil Kapoor  2 , Bal Krishna Mishra  2 , Anuj Gupta  2 , Bipinesh Sansar  2 , Vikash Pal  3 , Aparajita Pandey  2 , Avinash Bonda  3 , Indraja Siripurapu  3 , Vamshi Krishna Muddu  3 , Sadhana Kannan  4 , Deepali Chaugule  3 , Rajshree Patil  1 , Manali Parulekar  1 , Aditya Dhanawat  1 , Mehek Trikha  1 , Jaya Ghosh  1 , Vanita Noronha  1 , Nandini Menon  1 , Vijay Patil  5 , Kumar Prabhash  1 , Ian Olver  6
Affiliations
Clinical Trial

Olanzapine as Antiemetic Prophylaxis in Moderately Emetogenic Chemotherapy: A Phase 3 Randomized Clinical Trial

Vikas Ostwal et al. JAMA Netw Open. .

Abstract

Importance: The role of olanzapine has not been adequately evaluated in moderately emetogenic chemotherapy (MEC) regimens with or without neurokinin-1 receptor antagonists.

Objective: To evaluate whether addition of olanzapine to an MEC regimen reduces nausea, vomiting, and use of nausea rescue medications among patients with solid malignant tumors.

Design, setting, and participants: This multicenter, open-label phase 3 randomized clinical trial included patients aged 18 years or older with solid malignant tumors who were receiving oxaliplatin-, carboplatin-, or irinotecan-based chemotherapy. The trial was conducted at 3 institutes in India from March 26, 2019, to August 26, 2023; the final cutoff date for analysis was September 10, 2023.

Exposure: Patients were randomized 1:1 to dexamethasone, aprepitant, and palonosetron with olanzapine (experimental group) or without olanzapine (observation group). The experimental group received 10 mg of olanzapine orally once at night on days 1 through 3 of the chemotherapy regimen.

Main outcomes and measures: The primary end point was complete response (CR), defined as the proportion of patients with no vomiting, no significant nausea (scored as <5 on a visual analog scale of 1 to 100), and no use of rescue medications for nausea. Secondary end points included the proportion of patients experiencing nausea and chemotherapy-induced nausea and vomiting (CINV), receiving rescue medications, and experiencing adverse events.

Results: A total of 560 patients (259 [64%] male; median age, 51 years [range, 19-80 years]) were randomized. The analysis included 544 patients with evaluable data (274 assigned to olanzapine and 270 to observation). Baseline characteristics were evenly matched between the 2 groups. The proportion of patients with CR was significantly greater in the group with (248 [91%]) than without (222 [82%]) olanzapine in the overall 120-hour treatment period (P = .005). Likewise, there were significant differences between the olanzapine and observation groups for nausea control (264 [96%] vs 234 [87%]; P < .001) and CINV (262 [96%] vs 245 [91%]; P = .02) during the overall assessment period, and the proportion of patients receiving rescue medications significantly increased in the observation group (30 [11%]) compared with the olanzapine group (11 [4%]) (P = .001). Grade 1 somnolence was reported by 27 patients (10%) following administration of chemotherapy and olanzapine and by no patients in the observation group.

Conclusions and relevance: In this randomized clinical trial, the addition of olanzapine significantly improved CR rates as well as nausea and vomiting prevention rates in chemotherapy-naive patients who were receiving MEC regimens containing oxaliplatin, carboplatin, or irinotecan. These findings suggest that use of olanzapine should be considered as one of the standards of care in these chemotherapy regimens.

Trial registration: Clinical Trials Registry-India (CTRI) Identifier: CTRI/2018/12/016643.

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Conflict of interest statement

Conflict of Interest Disclosures: Prof Ostwal reported receiving grants from Dr Reddy’s Laboratories, Zydus Cadila, Intas Pharmaceuticals, and Indian Association for Supportive Care in Cancer to the institute for the study; nonfinancial support (olanzapine provided for the study) from Alkem Pharma during the conduct of the study; travel and logistic support to the institute for data presentation and advisory meetings from AstraZeneca, Intas Pharmaceuticals, and Natco; and honoraria to the institute for advisory meetings from Panacea, Zydus, Lupin, Servier, Mankind, Natera, Glenmark, MSD, and Predomics outside the submitted work. Dr Bhargava reported receiving grants from Reliance Life Sciences, Dr Reddy’s Laboratories, Emcure Pharmaceuticals, the Nag Foundation, Zydus Lifesciences, Intas Pharmaceuticals, and BDR Pharmaceuticals during the conduct of the study. Dr Ghosh reported receiving grants to the institution from Zydus Lifesciences and Dr Reddy’s Laboratories during the conduct of the study. Dr Menon reported receiving speaker fees from BMS outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. CONSORT Diagram
CINV indicates chemotherapy-induced nausea and vomiting; MEC, moderately emetogenic chemotherapy.
Figure 2.
Figure 2.. Test of Interactions on Complete Response (CR) Rates and Type of Chemotherapy Regimen
OR indicates odds ratio.
See this image and copyright information in PMC

References

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