Abstract P5-11-15: Rolapitant for the prevention of chemotherapy-induced nausea and vomiting in breast cancer patients receiving multiple cycles of emetogenic chemotherapy
Authors: Schwartzberg L , Navari R , Arora S , Powers D , Jordan K , Rapoport B 
Published: May 2019

Background: Patients (pts) with breast cancer often receive highly emetogenic chemotherapy, such as anthracycline plus cyclophosphamide (AC). Additionally, young age and female gender are risk factors for chemotherapy-induced nausea and vomiting (CINV) in response to emetogenic chemotherapy. We assessed the ability of the long-acting neurokinin-1 receptor antagonist (RA), rolapitant, in the prevention of CINV over multiple cycles in pts with breast cancer

Methods: This is a post hoc analysis of the prevention of CINV in a subset of pts with breast cancer from 3 similarly-designed, randomized, placebo-controlled phase 3 trials in which pts received a single oral dose of 180 mg rolapitant or placebo before chemotherapy. All pts received an oral 5-HT3 RA + dexamethasone (active control). The regimens were cisplatin-based (n=36), AC-based (n=681) or other (n=166; carboplatin, cyclophosphamide, etc). Pts who completed cycle 1 could continue the same antiemetic treatment in multiple cycles. Endpoints for cycle 1 of chemotherapy included complete response (CR; no emesis and no use of rescue medication) and no emesis, and no nausea (maximum visual analogue scale [VAS] &lt;5 mm), in the overall (0–120 h), acute (≤24 h), and delayed (&gt;24–120 h) phases. On days 6-8 of each subsequent chemotherapy cycle, pts self-reported the incidence of emesis or nausea interfering with normal daily life.

Results: In cycle 1, CR in both the overall (62.9% rolapitant, 55.1% control; p=0.018) and delayed (66.7% rolapitant, 59.7% control; p=0.032) phases were higher with rolapitant vs control . Rolapitant also improved no emesis rates in the overall (74.4% rolapitant, 62.6% control; p&lt;0.001) and delayed (77.2% rolapitant, 68.5% control; p=0.004) phases. Although less pts were available for follow up over multiple cycles, a numerically greater proportion of rolapitant-treated pts than control pts reported no emesis (cycles 2-6) and no interfering nausea (cycles 2-5) (table). The incidence of treatment-emergent adverse events (TEAEs) was similar for rolapitant (85.2%) and control (83.2%) during cycles 1-6. The most common TEAEs occurred at comparable rates in the rolapitant and control arms: fatigue (28.5% and 29.4%, respectively), alopecia (28.5% and 31.2%, respectively), and constipation (20.0% and 20.9%, respectively).

Conclusions: Rolapitant added to 5-HT3 RA and dexamethasone therapy improved CINV control and was safe and well-tolerated in pts with breast cancer receiving multiple cycles of emetogenic chemotherapy, mostly AC and carboplatin, historically a high-risk population for CINV.

 Pt-Reported Response in Multiple Cycles, % (n/N)* No Emesis  No Interfering Nausea  CycleRolapitant 180 mgActive Controlp-value *Rolapitant 180 mgActive Controlp-value *288.3 (323/366)80.0 (308/385)0.00271.6 (262/366)68.3 (263/385)0.329390.5 (297/328)80.5 (293/364)&lt;0.00173.8 (242/328)65.9 (240/364)0.025487.5 (266/304)82.4 (277/336)0.07579.3 (241/304)72.0 (242/336)0.033594.9 (111/117)88.2 (127/144)0.05987.2 (102/117)80.6 (116/144)0.152695.3 (102/107)88.9 (120/135)0.07184.1 (90/107)83.0 (112/135)0.811* Unstratified Cochran-Mantel-Haenszel test for between rolapitant and control difference in response rate.

Citation Format: Schwartzberg L, Navari R, Arora S, Powers D, Jordan K, Rapoport B. Rolapitant for the prevention of chemotherapy-induced nausea and vomiting in breast cancer patients receiving multiple cycles of emetogenic chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-11-15.