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

Table 2 Efficacy and safety outcomes

Ref.	Comparator regimen	Primary outcome (CR) definition	Acute CR (%)	Delayed CR (%)	Overall CR (%)	Nausea control (%)	Vomiting control (%)	Sedation/somnolence (%)	Other AEs (≥ 10%)	Statistical significance (P value/ 95%CI)	Relative risk/OR (95%CI)
Maleki et al[1], 2020	Mirtazapine + aprepitant + dexamethasone + granisetron (both arms NK1)	No vomiting + no rescue (0-120 hours)	76.6	86.6	63.3	70.0	86.6	53.3 (G1-3)	Fatigue 667; dry mouth 33.3; constipation 26.7; appetite loss 43.3	CR: P = 0.51-0.78; Somnolence P = 0.04; fatigue P = 0.02; FLIE P = 0.044
Radhakrishnan et al[38], 2020	Metoclopramide (no NK1)	No vomiting or nausea within 72 hours post rescue	70	100	72	59	72	25 (G1-3)	Anorexia 30 vs 27; abdominal pain 30 vs 24; headache 17 vs 10	Vomiting CR P = 0.003; nausea CR P = 0.026; sedation P = 0.0004	OR vomiting 4.0 (1.6-10.0); OR nausea 27 (1.1-6.6)
Wu et al[36], 2020	Tropisetron + dexamethasone (dual; no NK1)	No vomiting + no rescue (0-120 hours)	85.0	75.0	70.0	No nausea < 5 mm: 55		47.5	Constipation 62.5; anorexia 575; insomnia 15; dizziness 30	Delayed CR P = 0.044; overall CR P = 0.028; somnolence P = 0.001	OR overall CR ≈ 2.6; OR delayed ≈ 2.5
Sakai et al[17], 2021	None (single arm)	No emesis + no rescue (0-120 hours)	100	94	94	Total control 86	94	76 (mostly G1)	Constipation 72; dry mouth 64; insomnia 56; hiccups 50	P < 0.0001 vs historical 65% CR
Gao et al[10], 2022	Olanzapine + tropisetron + dexamethasone	No vomiting + no rescue (0-120 hours)	100	76	76	28.8	93.2	57.6	Fatigue 542; constipation 22	Acute CR P = 0.045; no vomiting P = 0.038	RR ≈ 1.13 (ns)
Liu et al[39], 2022	Aprepitant + tropisetron + dexamethasone	No vomiting + no rescue; TP primary	96.15 vs 97.17	75 vs 79.25	75 vs 79.25	TP 54.8 vs 54.7; TC 31.7 vs 27.3		88.46 vs 50.8	Constipation 53 vs 62	CR P = 0.46; somnolence P = 0.00; constipation P = 0.02
Yip et al[18], 2023	NEPA + dexamethasone	No vomiting + no rescue (0-120 hours)	70.0	92.9	65.0	91.7	68.3		Neutropenia ≥ G2↑ in olanzapine arm	Overall CR P = 0.5716; no nausea P = 0.0408
Navari et al[9], 2023	Olanzapine + 5-HT3 RA + dex + NK1 vs placebo	No emesis + no rescue (0-120 hours)		55 vs 47	55 vs 47	38 vs 30		Higher in NK1 arm (P = 0.017)	Appetite↑ (no difference)	Overall CR P = 0.0497; no nausea P = 0.2443	Risk difference +8% (both CR and nausea)
Zhao et al[29], 2023	Aprepitant + palonosetron + dexamethasone	No emesis + no rescue (0-120 hours)	88.9 vs 88.4	80.1 vs 79.9	78.1 vs 77.7	No nausea < 5 mm: 52 vs 50.6			None ≥ 10%	CR P = 0.765; 95%CI: -5.7 to 6.6	Risk difference +0.4%
Inui et al[11], 2024	Placebo + aprepitant + 5-5-HT3 RA + dex	No vomiting + no rescue	98.9 vs 97.8	87.4 vs 80.6	86.9 vs 80.6	No nausea 886		24.6 vs 22.9	Constipation 44; hepatotoxicity 55; cytopenias > 60	CR P = 0.116; nausea P < 0.001	Risk difference CR +6.3%; nausea +13.6%
Ostwal et al[37], 2024	Aprepitant + palonosetron + dex (NK1 triplet)	No vomiting + no nausea < 5 mm + no rescue (0-120 hours)	96	92	91	96	95	10 (G1)	None ≥ 10%	Overall CR P = 0.005; somnolence P < 0.001	OR CR 2.04 (1.24-3.36); OR nausea 3.57 (1.94-6.57)
Shen et al[20], 2024	Palonosetron + dexamethasone (dual; no NK1)	CR: No vomiting + no rescue; TP ≤ 25 mm; TC ≤ 5 mm	84.3	80.3	76.5	TP 66.7; TC 31.4		52.9	Appetite loss 56.9; weakness 78.4; dizziness 43.1	TP P = 0.003; drowsiness P = 0.027; FLIE P = 0.003	OR overall TP ≈ 3.3
Bhargave et al[15], 2025	Fosaprepitant + ondansetron + dex	CR: No vomiting + no rescue; primary: No nausea	87.3 vs 92.5	67.7	65.7 vs 66.7	No nausea 441		48.5 vs 29.0	Fatigue 28; muscle pain 19; constipation 15	No nausea P = 0.19; CR P > 0.99	OR no nausea 151 (0.84-2.69); CR 0.96 (0.53-1.73)
Attili et al[21], 2025	Placebo + granisetron + dex (no NK1)	No vomiting + no rescue	87.1	71.8	66.6	No nausea: 76.9 (acute), 46.1 (overall)		30.7 (mild)	Appetite↑ 10.2	Acute CR P = 0.001; overall CR P = 0.004	RR CR ≈ 1.95; RR Nausea ≈ 2.51

Complete response (no vomiting and no rescue medication). NK1: Neurokinin-1; NEPA: Netupitant-palonosetron; 5-HT₃ RA: 5-hydroxytryptamine 3 receptor antagonist; dex: Dexamethasone; CR: Complete response; TP: Total control (no vomiting + no rescue + nausea ≤ 25 mm); TC: Total control (nausea ≤ 5 mm); AE: Adverse events; FLIE: Functional Living Index-Emesis; CI: Confidence interval; OR: Odds ratio; RR: Relative risk; ns: Not significant.