Olanzapine-based vs neurokinin-1 receptor antagonist antiemetic regimens in highly emetogenic chemotherapy: Systematic review and meta-analysis of efficacy and safety

Table 1 Characteristics of included studies

Ref.	Country	Design	n	Cancer type	Chemo (HEC/MEC)	Intervention (olanzapine regimen)	Comparator	Olanzapine dose and duration	Follow-up	Key findings
Maleki et al[1], 2020	The Islamic Republic of Iran	Phase III, RCT, DB	60	Early breast (I-III)	AC (doxorubicin ≥ 50 + cyclophosphamide ≥ 500 mg/m2)	OLA 10 mg + aprepitant + dex + granisetron	Mirtazapine 15 mg + aprepitant + dex + granisetron	10 mg D1-4 (5 mg ≥ 60 years)	0-120 hours × 2 cycles	CR similar (acute 766% vs 83.3%); ↑somnolence/fatigue with OLA; better QoL (cycle 2) with mirtazapine
Radhakrishnan et al[38], 2020	India	Phase III, open-label RCT	80	Pediatric solid tumors	Mostly HEC (cisplatin/ifosfamide/cyclophosphamide/doxorubicin)	OLA (2.5-5 mg daily)	Metoclopramide (no NK1)	2.5-5 mg ≥ 72 hours	72 hours + AE 7 days	CR vomiting 72% vs 39%, nausea 59% vs 34%; sedation 25% vs 0%; OLA superior for breakthrough CINV
Wu et al[36], 2020	China	Retrospective cohort	93	GI (CRC 78.5%, gastric 21.5%)	MEC (mFOLFOX6/XELOX/FOLFIRI)	OLA 5 mg + tropisetron + dex	Tropisetron + dex	5 mg D1-3	0-120 hours	Overall CR 70% vs 47%; delayed CR 75% vs 55%; ↑QoL (75% vs 49% no impact); somnolence 47% vs 15%
Sakai et al[17], 2021	Japan	Phase II, single-arm	50	Thoracic (NSCLC 66%, SCLC 22%)	Carboplatin ± other drugs (HEC)	OLA 5 mg + granisetron + dex	None	5 mg D1-4 pm	0-120 hours	CR 100% acute, 94% delayed; no ≥ G3 AEs; nausea peaked D3-4
Gao et al[10], 2022	China	RCT	120	Lung (52%) + others	Cisplatin × 3 days (HEC)	Quadruple: OLA 5 mg + aprepitant + tropisetron + dex	Triplet: OLA 5 mg + tropisetron + dex	5 mg D1-3	0-120 hours (5 days)	Acute CR↑ (100% vs 93%, P = 0.045); overall CR NS; longer TTE with aprepitant; well-tolerated
Liu et al[39], 2022	China	RCT	210	Mixed solid tumors	Cisplatin × 3 days	OLA 5 mg + tropisetron + dex 10 mg	Aprepitant + tropisetron + dex 5 mg	5 mg D1-4	0-120 hours	Similar efficacy (all endpoints); somnolence (OLA) vs constipation (aprepitant)
Yip et al[18], 2023	Mainland	Post hoc (2 prospective)	120	Early breast	AC (HEC)	OLA 10 mg + aprepitant + ondansetron + dex	NEPA + dex	10 mg D1-5	0-120 hours × 4 cycles	C1: ↑“No rescue” and “no nausea”; CR similar (approximately 65%-70%); later cycles favored NEPA; QoL NS
Navari et al[9], 2023	United States	Phase III, RCT, DB, PC	690	Breast 77% + others	HEC (AC 77%, cisplatin 23%)	OLA + 5-HT3 RA + dex + placebo	Same + NK1 (fosaprepitant/aprepitant)	10 mg D1-4	0-120 hours × 4 cycles	Overall CR 47% vs 55%; NK1 arm better nausea control; OLA alone non-inferior not met; ↑sedation day 1
Zhao et al[29], 2023	China	Phase III, RCT, DB	720	Solid tumors	Cisplatin ≥ 50 mg/m2 (HEC)		Fosaprepitant vs aprepitant (+ palonosetron + dex)		0-120 hours	Fosaprepitant non-inferior for overall CR (78% vs 78%); similar nausea QoL; AEs mild
Inui et al[11], 2024	Japan	Phase III, RCT, DB, PC	355	Thoracic	Carboplatin ± ICI (HEC)	OLA 5 mg + aprepitant + 5-HT3 RA + dex	Placebo + same	5 mg D1-4 pm	0-120 hours	Overall CR 87% vs 81% (NS); no nausea↑ (89% vs 76% P < 0.001); somnolence 24%; no serious AEs
Ostwal et al[37], 2024	India	Phase III, open-label	544	Solid tumors (GI > lung)	MEC (oxaliplatin 61%, carbo 29%)	OLA 10 mg + aprepitant + palonosetron + dex	Aprepitant + palonosetron + dex	10 mg D1-3 hs	0-120 hours	Overall CR 91% vs 82% (P = 0.005); nausea 96% vs 87%; better QoL; somnolence 10% (G1)
Shen et al[20], 2024	China	RCT, open-label	102	GI (rectal 55%, gastric 28%)	MEC (XELOX/SOX/FOLFOX)	OLA 5 mg + palonosetron + dex	Palonosetron + dex	5 mg D1-5 hs	0-120 hours	TP 66.7% vs 37% (P = 0.003); QoL↑ (84% vs 59%); ↑drowsiness (53% vs 31%); ↑appetite
Bhargave et al[15], 2025	India	Phase III, DB, DD, PC	195	Head-neck 38%, Gyn 29% + others	Carboplatin AUC ≥ 4	OOD: OLA 5 mg + ondansetron + dex + placebo	Fosaprepitant + ondansetron + dex + placebo	5 mg D1-4	0-120 hours	Overall CR 66% vs 67% (NS); no nausea 44% vs 34%; sedation 49% vs 29%; cost-effective alternative
Attili et al[21], 2025	India	Phase III, RCT, DB, PC	82	Mixed carcinomas	Cisplatin-based HEC	OLA 10 mg + granisetron + dex	Placebo + granisetron + dex	10 mg D1 to D3	0-120 hours	CR↑ (acute 87% vs 55%, delayed 72% vs 47%, overall, 67% vs 34%); mild sedation 31%

Complete response (no vomiting and no rescue medication); total control (no vomiting + no rescue + nausea ≤ 25 mm). RCT: Randomized controlled trial; DB: Double-blind; PC: Placebo-controlled; DD: Double-dummy; GI: Gastrointestinal; CRC: Colorectal cancer; NSCLC: Non-small cell lung cancer; SCLC: Small cell lung cancer; Gyn: Gynecology; HEC: Highly emetogenic chemotherapy; MEC: Moderately emetogenic chemotherapy; AC: Doxorubicin, cyclophosphamide; mFOLFOX6: Modified fluorouracil, leucovorin, oxaliplatin 6-day regimen; XELOX: Capecitabine, oxaliplatin; FOLFIRI: Fluorouracil, leucovorin, irinotecan; ICI: Immune checkpoint inhibitor; XELOX: Capecitabine, oxaliplatin; SOX: S-1, oxaliplatin; FOLFOX: Fluorouracil, leucovorin, oxaliplatin; AUC: Area under the curve; OLA: Olanzapine; dex: Dexamethasone; 5-HT₃ RA: 5-hydroxytryptamine 3 receptor antagonist; NK1: Neurokinin-1; pm: Post meridiem; hs: Hora somni; AE: Adverse events; CR: Complete response; OLA: Olanzapine; QoL: Quality of life; CINV: Chemotherapy-induced nausea and vomiting; NS: Not significant; TTE: Time to emesis; C1: Cycle 1; NEPA: Netupitant-palonosetron; TP: Total control (no vomiting + no rescue + nausea ≤ 25 mm).