NO DIFFERENCE BETWEEN DEXAMETHASONE AND APREPITANT FOR DELAYED NAUSEA

In a phase III study reported in the Journal of Clinical Oncology, Roila et al compared aprepitant vs dexamethasone in prevention of delayed emesis in breast cancer patients treated with anthracycline/cyclophosphamide who had received palonosetron/aprepitant/dexamethasone prophylaxis for acute emesis. They found that the two agents had similar efficacy and toxicity.

Study Details

In this multicenter, double-blind trial, 551 chemotherapy-naive patients with breast cancer treated with anthracycline/cyclophosphamide (doxorubicin or epirubicin plus cyclophosphamide with or without fluorouracil [5-FU]) as adjuvant therapy or for metastatic disease received antiemetic prophylaxis with palonosetron at 0.25 mg IV, dexamethasone at 8 mg, and aprepitant at 125 mg prior to administration of chemotherapy. In addition, they were randomly assigned to receive dexamethasone at 4 mg twice daily (n = 273) or aprepitant at 80 mg once daily (n = 278) on days 2 and 3. The primary endpoint was rate of complete response, defined as no vomiting or rescue treatment, from days 2 to 5 after chemotherapy.

The aprepitant and dexamethasone groups were well balanced for age (median, 50 years in both; < 50 years in 43% and 46%, ≥ 65 years in 14% in both), Karnofsky performance status (100 in 99% in both), alcohol consumption (no for 83.5% and 77%), outpatient setting (99% in both), adjuvant therapy (97% and 98.5%), type of chemotherapy (5-FU, epirubicin, cyclophosphamide in 51% in both, epirubicin and cyclophosphamide in 41% in both, doxorubicin and cyclophosphamide in 8% in both), and concurrent drug treatment (benzodiazepines in 5% in both, opioids in 1% and < 1%, NSAIDs in 2% in both, and anti-H2 gastroprotectant drugs in 2% and 4%).

Acute Emesis Outcomes

After administration of the same prophylaxis in both groups, day 1 complete response rates were 84.9% in the aprepitant group and 87.6% in the dexamethasone group (P = .39). There were no significant differences in rates of complete protection (no vomiting, rescue treatment, or significant nausea), total control (no vomiting, rescue treatment, or nausea), no vomiting, no nausea, no significant nausea, or number of emetic episodes in those who vomited. There was borderline greater maximum severity of nausea (P = .07) and duration of nausea (P = .06) in the aprepitant group.

Aprepitant vs Dexamethasone in Delayed Emesis

Complete response rate from days 2 to 5 was 79.5% in both the aprepitant and dexamethasone groups (P = 1.00), and there were no significant differences in rates of complete protection (55% vs 60%), total control (43% vs 48%), no vomiting (89% vs 92%), no nausea (44% vs 49%), no significant nausea (57% vs 64%), mean number of emetic episodes (9.2 vs 5.7,  P = .07), maximum severity of nausea (45.5 vs 42.8 on visual analog scale) or mean duration of nausea (16.6 vs 14.1 hours). There was no difference between groups in impact of nausea and vomiting on quality of life as measured by the Functional Living Index-Emesis scale.

Adverse Events

The most common adverse events of any grade in the aprepitant group were asthenia (35% vs 33% in dexamethasone group), headache (18% vs 20%), and constipation (14% vs 19%) and among those in the dexamethasone group were asthenia, headache, constipation, epigastric pain (14% vs 9%), and face erythema (12.5% vs 8%). Insomnia (2.9 vs 0.4%, P = .02) and heartburn (8.1 vs 3.6%, P = .03) were significantly more common in the dexamethasone group. 

The investigators concluded, “In patients with breast cancer treated with anthracycline plus cyclophosphamide chemotherapy and receiving the same antiemetic prophylaxis for acute emesis, dexamethasone was not superior to aprepitant but instead had similar efficacy and toxicity in preventing delayed emesis.”

Fausto Roila, MD, of “S. Maria” Hospital, Terni, Italy, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by the Italian Minister of Health, Helsinn Health Care, and Italfarmaco. Dr. Roila has a consultant or advisory role with Merck Sharpe & Dohme and has received honoraria and research funding from Merck Sharp & Dohme.