FDA Approves Intravenous Rolapitant for CINV

Lee Schwartzberg, MD

The FDA has approved intravenous (IV) rolapitant (Varubi) for use in combination with other antiemetic agents to treat delayed chemotherapy-induced nausea and vomiting (CINV) in adults, according to TESARO, the manufacturer of the agent.

Delayed nausea and vomiting occurs between 25 and 120 hours after chemotherapy. The FDA previously approved oral rolapitant for this indication in September 2015. The IV approval was based on a bioequivalence trial that showed the comparability of the IV and oral formulations.

“Many healthcare providers tend to believe that CINV is no longer an unmet need but the reality is that more than half of patients treated with emetogenic chemotherapy experience delayed CINV, even when prescribed standard preventative therapies, such as a 5-HT3 receptor antagonist and dexamethasone,” Lee Schwartzberg, MD, professor of Medicine at University of Tennessee Health Science Center, said in a statement. “The FDA approval of Varubi IV gives doctors and nurses a new option to help protect their patients from these often preventable side effects.”

The bioequivalence study randomized healthy volunteers to a single dose of 166.5 mg of IV rolapitant administered over 30 minutes (n = 61) or 180 mg of oral rolapitant (n = 62). “Bioequivalence was defined by estimating whether the 90% confidence intervals for the ratio of the area under the curves of the two formulations are entirely included within the acceptance range of 80% to 125%,” TESARO explained in a press release. Other than infusion-site reactions with IV rolapitant, the safety profile in the study was consistent to previous trial findings with the oral formulation.

The efficacy of oral rolapitant was established based on 3 phase III clinical trials. Two studies, HEC1 and HEC2, evaluated rolapitant in patients receiving cisplatin-based highly emetogenic chemotherapy (HEC), the other looked at rolapitant in patients receiving moderately emetogenic chemotherapy (MEC).

Patients in both HEC trials received 180 mg oral rolapitant or placebo before HEC administration, as well as 10 μg/kg IV of the 5HT3-antagonist granisetron and 20 mg of oral dexamethasone on day 1, and 8 mg of oral dexamethasone twice daily on days 2 to 4 of the treatment cycle. A cycle lasted a minimum of 14 days, and patients could undergo up to 5 treatment cycles.

Complete response (CR) in the delayed phase of CINV, defined as 25 to 120 hours after the start of treatment, was 72.7% in the rolapitant arm compared with 58.4% for placebo (P <.001) in HEC1. In HEC2, CR was 70.1% for rolapitant compared with 61.9% for placebo (P = .043).

The most frequently reported adverse events (AEs) were neutropenia (9% with rolapitant vs 8% with control), hiccups (5% vs 4%), and abdominal pain (3% vs 2%).

Researchers evaluated the same dose of rolapitant in the MEC trial. As in the HEC trials, patients were assigned rolapitant or placebo prior to MEC, and both groups received granisetron and dexamethasone. MEC regimens included anthracycline/cyclophosphamide combinations, carboplatin, irinotecan, pemetrexed, oxaliplatin, and doxorubicin. The primary endpoint remained CR in the delayed phase of CINV.

CR was 71.3% in the rolapitant arm compared with 61.6% for patients receiving granisetron plus dexamethasone (P <.001). AEs occurring in ≥3% of patients were similar between the 2 groups, with the most common being decreased appetite (9% for rolapitant vs 7% for placebo), neutropenia (7% for rolapitant vs 6% for placebo), and dizziness (6% for rolapitant vs 4% for placebo).

Patients assigned to rolapitant also reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting over multiple cycles of chemotherapy.

“The approval of Varubi IV represents a significant milestone for TESARO. The majority of NK-1 receptor antagonist doses are administered intravenously in the United States, and with the introduction of Varubi IV, we now offer healthcare providers a unique, easy-to-use option that fits well into standard operating practices of a chemotherapy clinic or hospital,” Mary Lynne Hedley, PhD, president and COO of TESARO, said in a press release. “We will continue our efforts to expand awareness of delayed chemotherapy-induced nausea and vomiting, and plan to make this important medicine available next month.”

TESARO Announces U.S. FDA Approval of VARUBI® IV for Delayed Nausea and Vomiting Associated With Cancer Chemotherapy. TESARO. http://bit.ly/2gKXhgq. Accessed October 26, 2017.