Studies Confirm Rolapitant Reduces CINV in Breast and Gynecologic Cancers

Lee Schwartzberg, MD

Additional findings from 2 studies of rolapitant (Varubi) for the prevention of chemotherapy-induced nausea and vomiting (CINV) are providing further evidence of the efficacy of the long-acting NK-1 receptor antagonist. The research, presented during a poster session on Patient and Survivor Care at the 2016 ASCO Annual Meeting, evaluated the agent for use specifically in patients with breast and gynecologic cancers.

Lee Schwartzberg, MD, an author on both studies and director of the West Cancer Center at the University of Tennessee in Memphis, said that these follow-on analyses showed that the addition of rolapitant to the CINV regimen conferred a clinically meaningful benefit with no added toxicity: “Fewer patients had vomiting and fewer had to take rescue medicine. Overall, the quality of life was better for those patients.”

He added that women overall as well as younger women are more likely to experience CINV, providing a rationale for these targeted studies focused on subsets of women with either breast or gynecologic cancer. “We’ve known this [impact] for decades,” said Schwartzberg. “Having therapies for this particular side effect is really critical in these patients.”

Rolapitant is a potent, selective NK-1 receptor antagonist, with a plasma half-life of approximately 7 days. Activation of NK-1 receptors plays a central role in CINV induced by certain chemotherapies, particularly in the delayed phase after chemotherapy administration (>24—120 hours), which clinicians have found especially challenging to treat.

“By combining a steroid (dexamethasone), a serotonin 5-HT3 receptor antagonist, and an NK-1 receptor antagonist in what we call ‘triple therapy,’ you manage to control most of the vomiting,” said Bernardo Rapoport, a medical oncologist at The Medical Oncology Center of Rosebank in South Africa and also an investigator on the rolapitant trials.

CINV and AC-Based Breast Cancer Chemotherapy

For the first study,¹ investigators conducted a post-hoc analysis of a subgroup of patients with breast cancer drawn from a prior phase III rolapitant trial reported in Lancet Oncology.² Of the population included in this analysis (n = 845), 680 patients (80%) received anthracycline/cyclophosphamide (AC)—based chemotherapy, and 165 patients were treated with non–AC-based chemotherapy.

All patients were given granisetron (2 mg), along with dexamethasone (20 mg), both oral medications, and evenly randomized to receive either 180-mg oral rolapitant or a placebo 1 to 2 hours prior to chemotherapy on the first day of administration. The granisetron and dexamethasone regimen was administered 30 minutes prior to chemotherapy on day 1 with granisetron repeated once daily on days 2 and 3.

In the much smaller, non-AC group (20% of patients), investigators reported a trend toward better control of CINV with rolapitant versus placebo across all phases: overall (64.3% vs 60.5%; P = .616), acute (85.6% vs 82.7%; P = .598), and delayed (66.7% vs 64.2%; P = .740).

Results were comparable between the rolapitant and placebo arms on the endpoint of complete protection, defined as no emesis, no use of rescue medication, and no significant nausea. Schwartzberg explained that controlling nausea remains a significant unmet need in practice and is more difficult to quantify.

“Many people involved in the development of new chemotherapy-induced nausea and vomiting drugs believe that going forward, our goals for clinical trials should be the control of nausea. The bar would be set higher, because that’s the remaining need.”

Rolapitant in Women With Gynecologic Cancers

With younger age and female gender being known risk factors for CINV, this post-hoc subgroup analysis³ focused on women with ovarian, uterine, or cervical cancer (n = 201) participating in prior phase III rolapitant research.⁴

Investigators reported that CR rates were 9% to 16% higher with rolapitant versus placebo across all phases of CINV. CR during the overall phase was 79.2% with rolapitant compared with 63.2% in the control group (P = .012). During the acute phase, CR was 91.5% and 82.1%, respectively (P = .048), and in the delayed phase, CR was 80.2% and 64.2%, respectively (P = .011).

Additionally, rates of no emesis were 13% to 15% higher in patients receiving rolapitant and 20% better for those patients on the measure of no nausea during both the overall and delayed phases.

Study authors noted that some women with gynecologic cancer continued to have CINV, especially nausea. Insofar as nausea remains difficult to control, however, “improvements in rates of no nausea with the addition of rolapitant were notable.

References

1. Schwartzberg LS, Navari RM, Arora S, et al. Rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with breast cancer. J Clin Oncol. 2016;34 (suppl; abstr 10121).
2. Schwartzberg LS, Modiano MR, Rapoport BL, et al. Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens in patients with cancer: a randomised, active-controlled, double-blind, phase 3 trial. Lancet Oncol. 2015;16(9):1071-1078.
3. Rapoport BL, Schwartzberg LS, Arora S, et al. Rolapitant for control of chemotherapy-induced nausea and vomiting (CINV) in patients with gynecologic cancer. J Clin Oncol. 2016;34 (suppl; abstr 10122).
4. Rapoport BL, Chasen MR, Gridelli C, et al. Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: two randomized, active-controlled, double-blind, phase 3 trials. Lancet Oncol. 2015;16(9):1079-1089.

The investigators reported at ASCO that the addition of rolapitant yielded better results on the endpoint of complete response (CR) rates, defined as no emesis, no nausea, and no use of rescue medication. CR during the overall phase (0-120 hours) in the AC-based chemotherapy arm was 62.5% with rolapitant versus 53.9% with placebo (P = .024) and during the delayed phase was 66.7% and 58.8%, respectively (P = .034). Results were similar between study arms during the acute phase (≤24 hours), at 76.0% and 76.7%, respectively.