Investigating racial disparities in use of NK1 receptor antagonists to prevent chemotherapy-induced nausea and vomiting among women with breast cancer

e20506 Background: We have previously shown (dos Santos JNCI 2012) that NK1 receptor antagonists (NK1RA), such as aprepitant and casopitant, improve chemotherapy-induced nausea and vomiting (CINV) at the cost of increasing severe infection risk. Herein, we update our results. Methods: We searched MEDLINE, EMBASE, CENTRAL and meeting proceedings to identify randomized controlled trials (RCTs) comparing standard antiemetic therapy (dexamethasone + 5-HT3R inhibitors) versus NK1RA plus standard therapy for CINV prevention. Complete response (CR) was defined as absence of emesis and rescue therapy. The endpoints were CR post-chemotherapy in the overall phase (first 120 hours), CR in the acute phase (first 24 hours), and the delayed phase (24–120 hours), nausea, and toxicity. Subgroup analyses evaluated the type of NK1RA, the emetogenic potential of the chemotherapy, and prolonged use of 5-HT3R inhibitor. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Results: A total of 20 trials (9,935 patients) were included. NK1RA increased CR rate and nausea in all phases and subgroups. The CR in overall phase improved from 56% to 72% (OR = 0.52, 95% CI = 0.46 to 0.59, P < .00001, NNT=6). The side effects of NK1RA followed our previous report: the severe infection rate increased from 2.4% to 5.6% in the NK1RA group (four trials, 1656 patients; OR = 2.87; 95% CI = 1.58 to 5.19, P = .0005, NNH=31). Conclusions: NK1RA consistently improve CINV control in the acute, delayed, and overall phases, either for moderately or highly emetogenic chemotherapy regimens. Their use might be associated with increased infection rate, and a patient-level meta-analysis is warranted to clarify this safety issue.

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Mechanisms and latest clinical studies of new NK1 receptor antagonists for chemotherapy-induced nausea and vomiting: Rolapitant and NEPA (netupitant/palonosetron)

Cancer Treatment Reviews ◽

10.1016/j.ctrv.2015.09.005 ◽

2015 ◽

Vol 41 (10) ◽

pp. 904-913 ◽

Cited By ~ 16

Author(s):

Camilo Rojas ◽

Barbara S. Slusher

Keyword(s):

Clinical Studies ◽

Nausea And Vomiting ◽

Nk1 Receptor ◽

Receptor Antagonists ◽

Nk1 Receptor Antagonists

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Investigating racial disparities in use of NK1 receptor antagonists to prevent chemotherapy-induced nausea and vomiting among breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.7_suppl.292 ◽

2016 ◽

Vol 34 (7_suppl) ◽

pp. 292-292

Author(s):

Devon Check ◽

Katherine Elizabeth Reeder-Hayes ◽

Ethan M. Basch ◽

Leah L. Zullig ◽

Morris Weinberger ◽

...

Keyword(s):

Breast Cancer ◽

Black Women ◽

Racial Disparities ◽

Cancer Patients ◽

White Women ◽

Medicare Part D ◽

Nausea And Vomiting ◽

Medicare Part ◽

Nk1 Receptor ◽

Part D

292 Background: Chemotherapy-induced nausea and vomiting (CINV) is a major concern for cancer patients and, if uncontrolled, it can have serious implications for patients’ treatment outcomes, including quality of life. Guidelines recommend the use of an NK1 receptor antagonist to prevent CINV among patients beginning chemotherapy with a high risk of causing the side effect. However, barriers to use of oral NK1s (i.e., aprepitant) exist. In many cases, patients are required to fill a prescription for aprepitant at their home pharmacy. As well, the drug is expensive, costing over $500 under Medicare Part D, and patients may be responsible for a large portion of that cost. These barriers may contribute to racial disparities as they disproportionately affect minority patients. Methods: We used 2006-2012 SEER-Medicare data to evaluate the use of NK1s among black and white women initiating adjuvant chemotherapy with an anthracylcline and cyclophosphamide for early-stage breast cancer. NK1 use during the first chemotherapy cycle was measured using Medicare Part D and Part B claims. We used modified Poisson regression to assess the relationship between race and (1) any NK1 use, (2) oral NK1 (aprepitant) use, and (3) intravenous NK1 (fosaprepitant) use. We report adjusted risk ratios (aRR) and 95% confidence intervals (CI). Results: Of 1,015 eligible women (911 white; 104 black), 38% of white and 28% of black women received any NK1 at the start of their chemotherapy regimen. In adjusted analyses, black women were 30% less likely than white women to receive any NK1 (aRR black vs. white: 0.70, 95% CI: 0.52-0.94). This disparity was driven by a 44% gap in orally administered NK1s (aprepitant) (aRR: 0.56 95% CI: 0.35-0.89). We did not observe disparities in intravenous fosaprepitant use (aRR: 0.77, 95% CI: 0.46-1.28, NS). After controlling for variables related to socioeconomic status, disparities in NK1 and aprepitant use were reduced but not eliminated. Conclusions: Our study found racial disparities in women’s use of oral NK1s for the prevention of CINV. These disparities may be partly explained by racial differences in women’s ability to afford the medication.

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NK1 receptor antagonists and dexamethasone as anticancer agents in vitro and in a model of brain tumours secondary to breast cancer

Anti-Cancer Drugs ◽

10.1097/cad.0b013e32835ef440 ◽

2013 ◽

Vol 24 (4) ◽

pp. 344-354 ◽

Cited By ~ 10

Author(s):

Kate M. Lewis ◽

Elizabeth Harford-Wright ◽

Robert Vink ◽

Mounir N. Ghabriel

Keyword(s):

Breast Cancer ◽

Anticancer Agents ◽

Brain Tumours ◽

Nk1 Receptor ◽

Receptor Antagonists ◽

Nk1 Receptor Antagonists

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Current Trends and Future Directions in the Management of Delayed Nausea and Vomiting

European Oncology & Haematology ◽

10.17925/eoh.2013.09.2.84 ◽

2013 ◽

Vol 09 (02) ◽

pp. 84

Author(s):

Bernardo L Rapoport ◽

Georgia S Demetriou ◽

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Keyword(s):

Single Dose ◽

Receptor Occupancy ◽

Nausea And Vomiting ◽

Nk1 Receptor ◽

Binding Studies ◽

Receptor Antagonists ◽

Novel Approach ◽

Delayed Nausea ◽

Neurokinin 1 ◽

Nk1 Receptor Antagonists

The prophylaxis of chemotherapy-induced nausea and vomiting benefited greatly from the introduction of neurokinin-1 (NK1) receptor antagonists (RAs). Current emesis guidelines recommend that NK1 receptor antagonists be combined with 5-HT3 receptor antagonists and dexamethasone for highly emetic chemotherapy and moderately emetic chemotherapy. The first such medication, aprepitant, was approved in the US in 2003. Fosaprepitant, an intravenous prodrug of aprepitant, is also available as a single dose on day 1 in combination with other antiemetics. Fosaprepitant is rapidly converted to the active aprepitant and exhibits a similar half-life to orally administered aprepitant. In addition, receptor-binding studies have shown aprepitant striatal NK1 receptor occupancy of 90 % for over 48 hours after exposure. These characteristics may allow aprepitant, fosaprepitant and the newer NK1 RAs to be administered in a single dose on day 1. Olanzapine may prove to be a novel approach in the treatment of CINV, particularly in the management of nausea.

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