Reduced/No Dexamethasone With Netupitant/Palonosetron and Olanzapine for Chemotherapy‑Induced Nausea/Vomiting in Highly Emetogenic Chemotherapy: Phase III Noninferiority Trial

Author(s): Yanchun Meng, MD1,2; Yingying Liu, MD1,2; Mingxi Lin, MD2; Lili Wang, MD3; Yuxin Mu, MD1,2; Ling Yang, MD4; Yiqun Du, MD1,2; Xiaojun Liu, MD1,2; Yong Chen, MD5; Shaodong Tian, MD6; Qin Zhou, MD7; Xiaojie Zhuang, MD8; Zikang Li, MD9; Jinsong Liu, MD10; Shencun Fang, MD11; Weifei Fan, MD12; Yu Mao, MD13; Ling Zhang, MD14; Hao Wu, MD15; Fei Yan, MD16; Jie Weng, MD17; Jianhua Zhao, MD18; Xiangyu Long, MD19; Lianfang Liu, MD20; Jianbo Zhou, MD21; Jian Zhang, MD1,2;
Source: DOI: 10.1200/JCO-26-01029

Dr. Anjan Patel's Thoughts

This is a practical, easy-to-adopt result. In 644 patients on highly emetogenic chemotherapy, all getting NEPA plus olanzapine, a single 6 mg day-1 dex dose or no dex at all was noninferior to the standard 4-day course (complete response 72%, 72%, and 70%), with clearly less insomnia, hiccups, anxiety, and reflux. The day-1-only arm is the sweet spot, since going fully dex-free cost some early nausea control over days 1 to 3 before catching up. Caveats: it was open-label, only 6% were on concurrent immunotherapy, and the high-dose cisplatin subgroup was small, but for most of our HEC patients, olanzapine plus one day of dex looks like plenty.

PURPOSE

Guideline-recommended 4-day dexamethasone (DEX) for highly emetogenic chemotherapy (HEC) raises toxicity and immunotherapy interference concerns. We tested whether DEX reduction or omission with netupitant/palonosetron (NEPA) plus olanzapine (OLZ) is noninferior to standard DEX.

PATIENTS AND METHODS

In this open-label, randomized phase III noninferiority trial across 28 Chinese centers, adults receiving HEC received NEPA (day 1) plus OLZ (days 1-4) and were randomly assigned to standard DEX (12 mg day 1, 8 mg days 2-4), DEX-sparing (6 mg day 1 only), or DEX-free (no DEX). The primary end point was complete response (CR; no emesis/no rescue medication) from 0 to 120 h. Noninferiority margin was –12% (one-sided α = .025).

RESULTS

Of 644 randomly assigned patients (median age 54.9 years; 66.0% female), stratified analysis showed overall CR rates of 72.4% for standard, 72.2% for DEX-sparing (stratified risk difference [RD], –0.2% [95% CI, –8.7 to 8.5]; Pnoninferiority = .005), and 70.1% for DEX-free (stratified RD, –2.2% [95% CI, –10.7 to 6.4]; Pnoninferiority = .014). Both met noninferiority, confirmed in per-protocol analysis. Steroid-related toxicities were significantly lower with DEX-sparing and DEX-free regimens versus standard.

CONCLUSION

NEPA plus OLZ with reduced (6 mg day 1 only) or no DEX is noninferior to standard 4-day DEX for chemotherapy-induced nausea and vomiting prevention in HEC, supporting steroid-sparing strategies particularly relevant in the chemo-immunotherapy era.

Author Affiliations

1Phase I Unit, Fudan University Shanghai Cancer Center, Shanghai, China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; 3Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China; 4Department of Oncology, XinYu People's Hospital, XinYu City, China; 5Department of Medical Oncology, XINSTEEL Center Hospital, Xinyu City, China; 6Cancer Center, HuNan University of Medicine General Hospital, HuaiHua City, China; 7Thyroid and Breast Surgery Department, The First People's Hospital of KunShan, SuZhou City, China; 8Department of Medical Oncology, YiChun People's Hospital, YiChun City, China; 9Department of Oncology, YaAn People's Hospital, YaAn City, China; 10Department of Thoracic Tumor Surgery, XianTao First People's Hospital, XianTao City, China; 11Department of Medical Oncology, Nanjing Brain Hospital, NanJing City, China; 12Hematologic Oncology Department, JiangSu Province Official Hospital, NanJing City, China; 13Department of Medical Oncology, JiangShan People's Hospital, QuZhou City, China; 14Department of Oncology, Jintan Hospital, The Affiliated Hospital of Jiangsu University, ChangZhou City, China; 15Hematology-Oncology Department, The People's Hospital of LiuYang, ChangSha City, China; 16Department of Medical Oncology, Loudi Central Hospital, LouDi City, China; 17Department of Oncology, YueYang Central Hospital, YueYang City, China; 18Department of Oncology, The First People's Hospital of JingDeZhen, JingDeZhen City, China; 19Department of Oncology, Guang'an People's Hospital, Guang'an City, China; 20Department of Medical Oncology, Zhangjiagang Traditional Chinese Medicine Hospital, SuZhou City, China; 21Department of Medical Affairs, Fosun Yaohong (Jiangsu) Pharmaceutical Technology Co, Ltd, NanJing City, China

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