Extended-Release Anti-CINV Agent Effective in Patients Treated With Cisplatin

Jennifer A. Wenzel, PhD, RN, CCM, FAAN

Findings from a randomized trial reported at the 2016 Annual Meeting of the Society of Gynecologic Oncology showed that APF530, an extended-release formulation of the antiemetic granisetron, achieved a complete response more often than did ondansetron in patients receiving highly emetogenic cisplatin-based chemotherapy.

The percentage of patients who had complete response in the delayed phase of chemotherapy treatment was 64.8% with APF530 compared with 56.3% of patients assigned to the ondansetron arm of the study. Secondary endpoints—including complete response in the acute phase and overall, complete control, and total response—all favored the investigational antiemetic.¹

These findings are consistent with those of the overall trial, which reported a statistically significant improvement in complete response with APF530. As a post-hoc analysis, the results in the cisplatin-treated subgroup lacked statistical power to demonstrate significant differences between treatment groups.

“APF530 showed clinical benefit in delayed-phase complete response in patients receiving cisplatin-based highly emetogenic chemotherapy, a particularly difficult-to-manage regimen commonly used for gynecologic cancers,” Lee Schwartzberg, MD, a medical oncologist at the West Clinic in Memphis, Tennessee, and colleagues concluded in a poster presentation. “APF530 is the only 5-HT3 receptor antagonist to demonstrate superiority over another as part of the guideline-recommended regimen in a three-drug versus three-drug phase III efficacy trial.”

APF530 consists of 2% granisetron in a proprietary viscous bioerodible vehicle that undergoes controlled hydrolysis after administration to effect extended release of granisetron for prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). A single subcutaneous dose of APF530 has been shown to achieve and maintain therapeutic levels of granisetron for at least 5 days.²

Schwartzberg and colleagues reported findings from a subgroup analysis of the phase III MAGIC trial, which compared APF530 and ondansetron—each in combination with the neurokinin-1 receptor antagonist fosiprepitant and dexamethasone—in 942 patients receiving highly emetogenic chemotherapy regimens for cancer. The trial had a primary endpoint of complete response (CR), defined as no emesis and no use of rescue medication for CINV during the delayed phase (24-120 hours).

As reported at the 2015 meeting of the American Society of Clinical Oncology, the primary analysis showed that the APF530 treatment group had a significantly higher rate of CR: 64.7% vs. 56.6% (P = .014).

The post-hoc subgroup analysis comprised 251 patients treated with cisplatin-based chemotherapy, the most common combination being cisplatin plus gemcitabine (27.1%). The type of cancer for the indicated chemotherapy was not recorded.

As in the overall trial, the primary endpoint for the subgroup analysis was CR during the delayed phase. Secondary endpoints included CR in the acute phase and overall; complete control (CR plus no more than mild nausea); and total response (CR and no nausea).

The analysis yielded a primary outcome (8.5% absolute difference in favor of APF530) almost identical to that of the overall trial (8.0% absolute difference). Acute-phase complete response rates were 84.0% with APF530 and 80.2% with ondansetron, and overall complete response rates were 60.8% and 54.8%.

For the endpoint of complete control, all comparisons favored the APF530 group: delayed phase (61.6% vs 53.2%); overall (58.4% vs 50.8%), and acute phase (84.0% vs 76.2%). Total response rates were 48.0% for APF530 and 45.2% for ondansetron in the delayed phase, 48.0% versus 44.4% overall, and 81.6% versus 73.8% during the acute phase.

Among female patients treated with cisplatin-based chemotherapy (45% of the subgroup), most of the endpoints were numerically greater for APF530 as compared with the total subgroup. Absolute differences in complete response were 10.3% in the delayed phase, 10.0% overall, and 8.9% in the acute phase. A spokesperson for Heron Therapeutics said the company is awaiting final word from the FDA on an application for approval. The company is seeking approval for use of APF530 in the management of CINV associated with both highly emetogenic and moderately emetogenic chemotherapy regimens.

References

• Schwartzberg L, Mosier M, Payne Y, et al. Phase III trial of APF530 versus ondansetron, each with a neurokinin I antagonist and corticosteroid, for prevention of chemotherapy-induced nausea and vomiting in highly emetogenic chemotherapy regimens (MAGIC Trial): outcomes in cisplatin-based regimens. Presented at: 2016 SGO Annual Meeting. March 19-22, 2016. San Diego, CA. Abstract 5988.
• Gabrail N, Yanagihara R, Spaczynski M, et al. Pharmacokinetics, safety, and efficacy of APF530 (extended-release granisetron) in patients receiving moderately or highly emetogenic chemotherapy: results of two phase II trials. Cancer Manag Res. 2015; 7:83-92.