AT THE ANNUAL MEETING ON WOMEN’S CANCER

SAN DIEGO (FRONTLINE MEDICAL NEWS) – An investigational extended-release formulation of granisetron outperformed ondansetron as a component of triple-drug antiemetic therapy for patients on cisplatin-based highly emetogenic chemotherapy, Dr. Lee Schwartzberg reported at the annual meeting of the Society of Gynecologic Oncology.

He presented a post hoc subgroup analysis drawn from the previously reported pivotal phase III 942-patient MAGIC trial of extended-release granisetron (Sustol), formerly known as APF530, versus ondansetron (Zofran) as part of the triple-drug antiemetic regimen recommended in National Community Cancer Network guidelines for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients on highly emetogenic chemotherapy .

Dr. Schwartzberg and coinvestigators focused on the 251 MAGIC participants on high-dose cisplatin-based chemotherapy. The reason? Few studies have examined the management of CINV in patients on platinum-based regimens, commonly used in treating gynecologic cancers, explained Dr. Schwartzberg, medical director of the West Clinic in Memphis.

Sustol consists of 2% granisetron in a proprietary slow-release vehicle. A single 500-mg subcutaneous dose containing 10 mg of granisetron maintains therapeutic blood levels of granisetron for 5 days or longer. These pharmacokinetics make APF530 an attractive strategy for preventing both acute and delayed chemotherapy-induced nausea and vomiting. The delayed phase, which affects many cancer patients 2-5 days following administration of chemotherapy, has traditionally been a particularly difficult management challenge.

National Community Cancer Network guidelines recommend that patients on highly emetogenic chemotherapy receive a potent three-drug antiemetic regimen consisting of a 5-hydroxytryptoamine-3 receptor antagonist – ondansetron and granisetron fall within this class – along with a neurokinin-1 receptor antagonist and dexamethasone.

MAGIC was a double-blind, prospective, multicenter trial in which 942 patients on highly emetogenic chemotherapy received either 500 mg of subcutaneous extended-release granisetron or intravenous ondansetron at 0.15 mg/kg. In addition, all participants concomitantly got 150 mg of the neurokinin-1 receptor antagonist fosaprepitant (Emend) plus 12 mg of IV dexamethasone on day 1, followed by 8 mg of oral dexamethasone once on day 2 and 8 mg twice daily on days 3 and 4.

In the overall trial, extended-release granisetron significantly outperformed ondansetron. The primary endpoint – complete response defined as no emesis and no use of rescue medication for CINV during the delayed phase – was achieved in 64.7% of the Sustol group, compared with 56.6% on ondansetron.

Results in Dr. Schwartzberg’s post hoc analysis confined to the 251 randomized patients on high-dose cisplatin-based chemotherapy paralleled those in the overall trial: a 64.8% complete response rate in the delayed phase in the granisetron group versus 56.3% with ondansetron. That absolute 8.5% difference favoring the investigational agent translates to a number needed to treat (NNT) of 12.

In the 112 women on highly emetogenic cisplatin-based chemotherapy, the complete response rates in the delayed phase were 61.6% with extended-release granisetron and 53.2% with ondansetron, for an absolute 10.3% difference and an NNT of 10.

Heron Therapeutics, which is developing extended-release granisetron, is awaiting word from the Food and Drug Administration regarding the company’s application for marketing approval.

The MAGIC trial was sponsored by Heron Therapeutics. Dr. Schwartzberg is a consultant to the company.

bjancin@frontlinemedcom.com

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