APF530 versus ondansetron, each in a guideline-recommended three-drug regimen, for the prevention of chemotherapy-induced nausea and vomiting due to anthracycline plus cyclophosphamide–based highly emetogenic chemotherapy regimens: a post hoc subgroup analysis of the Phase III randomized MAGIC trial

Abstract

BackgroundAPF530, a novel extended-release granisetron injection, was superior to ondansetron in a guideline-recommended three-drug regimen in preventing delayed-phase chemotherapy-induced nausea and vomiting (CINV) among patients receiving highly emetogenic chemotherapy (HEC) in the double-blind Phase III Modified Absorption of Granisetron In the prevention of CINV (MAGIC) trial.Patients and methodsThis MAGIC post hoc analysis evaluated CINV prevention efficacy and safety of APF530 versus ondansetron, each with fosaprepitant and dexamethasone, in patient subgroup receiving an anthracycline plus cyclophosphamide (AC) regimen. Patients were randomized 1:1 to APF530 500 mg subcutaneously (granisetron 10 mg) or ondansetron 0.15 mg/kg intravenously (IV) (≤16 mg); stratification was by planned cisplatin ≥50 mg/m2 (yes/no). Patients were to receive fosaprepitant 150 mg IV and dexamethasone 12 mg IV on day 1, then dexamethasone 8 mg orally once daily on day 2 and twice daily on days 3 and 4. Patients were mostly younger females (APF530 arm, mean age 54.1 years, female, 99.3%; ondansetron arm, 53.8 years, female 98.3%). The primary end point was delayed-phase (>24–120 hours) complete response (CR).ResultsAPF530 versus ondansetron regimens achieved numerically better CINV control in delayed and overall (0–120 hours) phases for CR, complete control, total response, rescue medication use, and proportion with no nausea. APF530 trends are consistent with the overall population, although not statistically superior given the underpowered AC subgroup analysis. The APF530 regimen in this population was generally well tolerated, with safety comparable to that of the overall population.ConclusionAPF530 plus fosaprepitant and dexamethasone effectively prevented CINV among patients receiving AC-based HEC, a large subgroup in whom CINV control has traditionally been challenging.

Control of Nausea and Vomiting in Patients Receiving Anthracycline/Cyclophosphamide Chemotherapy for Breast Cancer

“…However, under such a condition, the control of CINV was insufficient: 48% for complete response, 32% for complete control, 32% for the rate of no nausea, and 48% for the rate of no significant nausea during overall period, although vomiting was well controlled (78% for no vomiting during overall period). The rates of control of CINV during overall period observed in the present study were generally consistent with those reported by other investigators in breast cancer patients receiving AC chemotherapy: the complete response rate was similar to the data (47%) by Yeo et al (12), that (50%) by Hesketh et al (14) and within a range (36-82%) reported by others (8,11,13,15,22,23). The rates of no nausea and no vomiting were also within the range reported by other investigators [31-49% for nausea (8)(9)(10)(11)(12); 55-92% for vomiting (9-12, 13-16)].…”

“…However, the control of CINV associated with AC chemotherapy is not necessarily sufficient, even when the guideline-consistent three-drug antiemetic premedication is implemented. Particularly, the rate of no nausea is too low (31-49%) (8)(9)(10)(11)(12) compared to the rate of no vomiting (55-92%) (9)(10)(11)(12)(13)(14)(15)(16). We also previously reported that AC chemotherapy for breast cancer is most emetogenic among various chemotherapy regimens that were carried out in the outpatient setting, in which the odds ratio (OR) for incidence of CINV is 4.955 [95% confidence interval (CI)=1.863-13.18; p=0.001] (17).…”

Recent advances in antiemetics: new formulations of 5HT₃-receptor antagonists

“… 54 In a post hoc subgroup analysis of the 589 patients (65%) receiving AC-based HEC, at least 98% of whom were women, delayed-phase CR rates showed a trend favoring the GERSC arm (64%) over the ondansetron arm (56%). 95 A similar trend was found in the subgroup of 252 patients scheduled to receive cisplatin, where delayed-phase CR rates were numerically higher in the GERSC arm (65%) than in the ondansetron arm (55%). 96 These subgroup findings were consistent with the overall population, although the analyses were not powered to show a significant difference between groups.…”

Phase IIIb Safety and Efficacy of Intravenous NEPA for Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Patients with Breast Cancer Receiving Initial and Repeat Cycles of Anthracycline and Cyclophosphamide (AC) Chemotherapy

“…Although there are inherent challenges in comparing results across trials, it is encouraging that the complete response rates in this (and the prior oral NEPA) study are higher than those seen for other NK 1 triplet regimens in the AC setting (e.g., overall complete response rates in phase III trials: oral aprepitant 51% , fosaprepitant (51%–56%) , and oral rolapitant 63% ). It is noteworthy that these NK 1 RAs were combined with first‐generation 5‐HT 3 RAs ondansetron (aprepitant/fosaprepitant trials) and granisetron (rolapitant trial).…”