Table 1.
Summary of studies for the prevention of CIN in patients treated with NK1RAs in phase III clinical trialsa
| Reference | Patients randomized | Chemotherapy regimen | Antiemetic prophylaxis | Proportion of patients with no significant nausea (%) | ||
|---|---|---|---|---|---|---|
| Acute | Delayed | Overall | ||||
| Aprepitant | ||||||
| Warr [17] | 866 | AC-HEC | APR + OND + DEX vs. PBO + OND + DEX | NA | NA | 61 vs. 56 |
| No nausea (%) 33 vs. 33 | ||||||
| Rapoport [18] | 848 | AC-HEC/MEC | APR + OND + DEX vs. PBO + OND + DEX | NA | NA | 73.6 vs. 66.4* |
| Hesketh [15] | 530 | HEC | APR + OND + DEX vs. PBO + OND + DEX | 90.6 vs. 86.5 | 75.3 vs. 68.5 | 73.2 vs. 66.0 |
| Poli-Bigelli [16] | 569 | HEC | APR + OND + DEX vs. PBO + OND + DEX | NA | 73 vs. 65 | 71 vs. 64 |
| No nausea (%) 52.7 vs. 39.9** | No nausea (%) 48.8 vs. 38.8* | |||||
| Schmoll [45] | 489 | HEC | APR + OND + DEX vs. PBO + OND + DEX | 92.1 vs. 89.5 | 75.9 vs. 72.1 | 73.1 vs. 69.7 |
| Fosaprepitant | ||||||
| Grunberg [46] | 2322 | HEC | FOS + OND + DEX vs. APR + OND + DEX | NA | NA | 70.1 vs. 70.4 |
| No nausea (%) 53.0 vs. 50.9 | ||||||
| Weinstein [47] | 1015 | MEC | FOS + OND + DEX (D1) vs. PBO + OND + DEX (D1) followed by OND (D2–3) | 83.1 vs. 78.3* | ||
| No nausea (%) 65.3 vs. 61.6 | ||||||
| Aprepitant / fosaprepitant in delayed nausea | ||||||
| Roila [48] | 580 | AC-HEC | Both arms APR + PAL + DEX (D1) followed by APR once-daily (D2–3) + PBO once daily (evenings) vs. DEX twice daily (D2–3) | 36.3 vs. 32.6 | 56.8 vs. 63.7 | NA |
| No nausea (%) 53.6 vs. 52.0 | No nausea (%) 43.9 vs. 49.1 | |||||
| Roila [49] | 284 | HEC | Both arms APR + PAL + DEX (D1) followed by APR (D2–3) + DEX (D2–4) vs. MTC (D2–4) + DEX (D2–4) | 87.8 vs. 89.8 | 77.6 vs. 81.0 | NA |
| No nausea (%) 80.3 vs. 86.9 | No nausea (%) 71.4 vs. 73 | |||||
| Rolapitant | ||||||
| Schwartzberg [44] | 1369 | AC–HEC/MEC | D1: ROL + GRAN + DEX vs. PBO + GRAN + DEX D2–3: GRAN | 82 vs. 85 | 73 vs. 69 | 71 vs. 67 |
| No nausea (%) 65 vs. 66 | No nausea (%) 48 vs. 45 | No nausea (%) 45 vs. 42 | ||||
| Rapoport [43] | 532 (Study 1) | HEC | D1: ROL + GRAN + DEX vs. PBO + GRAN + DEX D2–4: DEX | 86 vs. 79* | 73 vs. 65* | 72 vs. 63* |
| No nausea (%) 68 vs. 61 | No nausea (%) 53 vs. 42** | No nausea (%) 50 vs. 39* | ||||
| Rapoport [43] | 555 (Study 2) | HEC | D1: ROL + GRAN + DEX vs. PBO + GRAN + DEX D2–4: DEX | 90 vs. 86 | 75 vs. 69 | 73 vs. 68 |
| No nausea (%) 73 vs. 68 | No nausea (%) 58 vs. 47** | No nausea (%) 55 vs. 44** | ||||
| NEPA | ||||||
| Aapro [50] | 1455 | AC-HEC | NEPA + DEX (D1) vs. PAL + DEX (D1) | 87.3 vs. 87.9 | 76.9 vs. 71.3* | 74.6 vs. 69.1* |
| Grallab [51] | 413 | HEC/MEC | NEPA + DEXc + PBO vs. APR + PAL + DEXc | NA | NA | 84.1–92.3 vs. 80.8–86.5 cycles (1–6) |
| Heskethd [52] | 694 | HEC | NEPA300 (NETU300 + PAL) + DEX (D1–4) (N = 143) vs. PAL + DEX (D1–4) + PBO (N = 136) | 98.5 vs. 93.4* | 90.4 vs. 80.9* | 89.6 vs. 79.4* |
AC anthracycline plus cyclophosphamide, APR aprepitant, CIN chemotherapy-induced nausea, D day, DEX dexamethasone, FOS fosaprepitant, GRAN granisetron, HEC highly emetogenic chemotherapy, MEC moderately emetogenic chemotherapy, MTC metoclopramide, NA not available, NEPA netupitant (300 mg) plus palonosetron (0.5 mg), NETU netupitant, NK 1 neurokinin-1, OND ondansetron, PAL palonosetron, PBO placebo, RA receptor antagonist, ROL rolapitant
aNausea was not the primary endpoint of these phase III trials
bNo formal testing was performed for between-group comparisons
cDexamethasone was administered on days 1–4 in patients receiving HEC and on day 1 in patients receiving MEC
dPhase II pivotal study. NEPA100/NEPA200/NEPA300 + DEX doses were analyzed. Only data from NEPA300 + DEX vs. PAL + DEX are presented
*p ≤ 0.05;**p ≤ 0.01