As part of a three-drug regimen, APF530 (extended-release formulation of granisetron) has become the first 5-HT3 (5-hydroxytryptamine) receptor antagonist to demonstrate superiority over the standard of care for delayed nausea and vomiting after highly emetogenic chemotherapy. According to the results of the MAGIC trial, presented at the 2015 Breast Cancer Symposium, APF530, administered with fosaprepitant (Emend) and dexamethasone, provided superior complete response in delayed-phase chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy vs a standard-of-care regimen of ondansetron with fosaprepitant plus dexamethasone.1
“The APF530 regimen was associated with a clinical benefit over the ondansetron regimen in nausea control, rescue medication use, and patient satisfaction,” said Ian D. Schnadig, MD, of Compass Oncology, US Oncology Research, Tualatin, Oregon. “It is significant that both arms of the study had a three-drug prophylactic regimen, which has not been previously evaluated in phase III trials in this high-risk patient group.”
“Results presented here indicate that not all 5-HT3 receptor antagonists are equally effective in the setting of delayed-phase chemotherapy-induced nausea and vomiting due to highly emetogenic chemotherapy,” Dr. Schnadig added.
Although APF530 has been previously tested in randomized trials—demonstrating noninferiority to palonosetron in various settings—the MAGIC trial is the first three-drug vs three-drug regimen efficacy trial, based on current antiemetic guideline–recommended treatment, comparing the efficacy and safety of APF530 in preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy with ondansetron.
MAGIC Trial
The MAGIC trial is a prospective, randomized, placebo-controlled, double-dummy, double-blind, multicenter trial conducted in the United States. Researchers stratified 942 patients based on planned receipt of cisplatin (yes or no) before randomization to one of two arms.
In the ondansetron arm, patients received ondansetron (0.15 mg/kg IV), fosaprepitant (150 mg IV), dexamethasone (12 mg IV), and placebo subcutaneous injection. In the APF530 arm, patients received fosaprepitant (150 mg IV), dexamethasone (12 mg IV), and APF530 (500-mg subcutaneous injection).
The study’s primary endpoint was the proportion of patients achieving a complete response, which was defined as no emetic episodes (vomit or retch) and no rescue medication use during the delayed-onset phase of chemotherapy-induced nausea and vomiting, occurring 24 to 120 hours following administration of highly emetogenic chemotherapy agents.
Demographics were balanced between the treatment arms, Dr. Schnadig noted, with the majority of patients being female. The most common chemotherapy regimens in both treatment arms were AC-based (anthracycline-cyclophosphamide) regimens, representing almost two-thirds of patients.
Primary Endpoint Met
As Dr. Schnadig reported, the study met its primary endpoint. “The percentage of patients who achieved a complete response was significantly higher in the APF530 group than the ondansetron group (64.7% vs 56.6%, P = .014),” he said. “Complete response rates were 8.0% higher in the APF530 arm, equating to a 14.2% relative improvement.”
In addition, for those patients receiving cisplatin, the results were even more impressive. “Within the cisplatin stratum,” he added, “complete response rates were 10.6% higher in the APF530 arm compared to the ondansetron arm, equating to a 19.4% relative improvement and indicating a meaningful clinical benefit in this particularly difficult-to-treat patient population.”
The following trends favoring APF530 over ondansetron were also observed:
- The percentage of patients who achieved complete control, defined as complete response plus no more than mild nausea during the delayed-onset phase, favored APF530 (P = .022);
- Overall-phase complete response rates were 58.4% and 52.9% in the APF530 and ondansetron arms, respectively;
Rates of no emetic episodes were 82.2% and 79.2% in the APF530 and ondansetron arms, respectively.
According to Dr. Schnadig, a significantly greater proportion of patients in the APF530 arm did not require rescue medication in the delayed phase vs ondansetron (P = .013). Patient-reported satisfaction with nausea and vomiting control was also significantly better with APF530 vs ondansetron in the delayed phase (P = .040), and the proportion of patients with treatment failure was numerically higher across the entire treatment period with ondansetron (P = .095).
APF530 was generally well tolerated, Dr. Schnadig noted, with no new safety signals identified. The most common treatment-emergent adverse events were injection-site reactions, which were generally mild or moderate.
“Symptom management in patients receiving cancer treatment represents a significant unmet medical need,” concluded Dr. Schnadig, “and the results of this study represent another step forward in this important clinical space.” ■
Disclosure: Research support for this study was provided by Heron Therapeutics. Dr. Schnadig is employed by Compass Oncology and reported relationships with Heron, Tesaro, and McKesson.
Reference
1. Schnadig ID, Agajanian R, Dakhil SR, et al: Phase III study of APF530 versus ondansetron with a neurokinin 1 antagonist + corticosteroid in preventing highly emetogenic chemotherapy-induced nausea and vomiting: MAGIC trial. 2015 Breast Cancer Symposium. Abstract 68. Presented September 25, 2015.
