Τρίτη, 10 Νοεμβρίου 2015

NEPA ADDED IN ASCO ANTIEMETIC GUIDELINES

The new antiemetic combination product containing netupitant and palonosetron (known as NEPA and marketed as Akynzeo , Helsinn/Eisai), has been included in the guidelines on antiemetic use in cancer patients receiving chemotherapy issued by the American Society of Clinical Oncology (ASCO).
This is an expedited update of the 2011 guidelines, notes ASCO, specifically made to incorporate guidance on the use of this new product. The remainder of the guidelines is unchanged pending a full review.
NEPA was approved for use in the United States in October 2014.
The new update to the guidelines was published onlineNovember 2 in the Journal of Clinical Oncology.
It states that all cancer patients who receive highly emetogenic chemotherapy regimens (including anthracycline plus cyclophosphamide) should be offered a three-drug combination of an NK1 receptor antagonist, a 5-HT3 receptor antagonist, and dexamethasone.
Available NK1 receptor antagonists include aprepitant and fosaprepitant; available 5HT3 antagonists include granisetron, ondansetron, palonosetron, dolasetron, tropisetron, and ramosetron.
"The oral combination of NEPA plus dexamethasone is an additional treatment option in this setting,” the updated guideline states.
The NEPA combination comprises a new NK1-antagonist, netupitant, and an older 5HT3-antagonist, palosetron (which was approved as a single agent in 2008).
Evidence for NEPA's efficacy in preventing chemotherapy-induced nausea and vomiting comes from two phase 3 clinical trials involving a total of 1720 participants receiving cancer chemotherapy, both of which were published in the Annals of Oncology and reported at the time by Medscape Medical News.
In the new update to the ASCO guidelines, the authors, headed by Paul J. Hesketh, MD, Lahey Hospital and Medical Center, Burlington, Massachusetts, provide a summary of the findings.
One of these phase 3 trials was conducted in 1449 patients receiving anthracycline plus cyclophosphamide chemotherapy for solid tumors. Patients in both arms of the study received dexamethasone on day 1 only and the were randomly assigned to receive NEPA plus dexamethasone or palonosetron and dexamethasone (this control group was specified by regulatory agencies, the guideline authors note).
Compared with palonosetron, NEPA resulted in higher rates of complete response (no emesis or rescue medication) during both the acute phase (within 24 hours of receiving chemotherapy) and the delayed phase (from 25 to 100 hours after receiving chemotherapy). The secondary end points of no emesis, no significant nausea, and complete protection (complete response and no significant nausea) were also better in the NEPA arm.
The safety profile of NEPA was generally similar to that of palonosetron, the guideline authors note. A severe adverse event was reported by 94 of 725 patients in the NEPA arm, but only five patients (0.7%) had a severe treatment-related adverse event. The most common treatment-related adverse events were headache (NEPA arm, 3.3%; palonosetron arm, 3.0%) and constipation (both arms, 2.1%).
The other phase 3 trial was conducted in 413 chemotherapy-naive patients treated with highly or moderately emetogenic chemotherapy. Patients with breast cancer treated with anthracycline plus cyclophosphamide chemotherapy were not eligible for this trial.
In this trial, the control arm received oral aprepitant plus oral palonosetron. The guideline authors note that in this trial, only descriptive statistics were provided, and there was no formal testing of between-group differences. The rate of complete response with NEPA remained high across chemotherapy cycles, they note, commenting that NEPA was "effective in preventing nausea and vomiting."
Treatment-emergent adverse events occurred in 86% of patients in the NEPA arm and 91.3% of patients in the aprepitant plus palonosetron arm; a majority of these events were mild or moderate. Adverse effects that were considered to be related to the study drug occurred in 10.1% of patients in the NEPA arm and 5.8% of patients in the aprepitant plus palonosetron arm. The most common treatment-related adverse events in the NEPA arm were constipation (3.6%) and headache (1.0%). Only one adverse event was classified as severe and possibly related to antiemetic treatment: a patient in the NEPA arm experienced acute psychosis in cycle one and discontinued treatment. This event was also thought to be possibly related to dexamethasone.
Cost-effectiveness to Be Explored Soon
"Formal cost-effectiveness analyses of NEPA are not yet available," the guideline authors write. However, they point out that because NEPA is an all-oral regimen, it will require patients to both fill and pay for a prescription. The out-of-pocket cost will vary by insurance plan, and this point should be discussed with patients, the authors note.
How the new product fits with respect to the cost and effectiveness of other antiemetic options "will be explored more fully in the planned, comprehensive update of the ASCO antiemetic guideline.
"Of particular interest are emerging data on the psychotropic medication olanzapine. Olanzapine is inexpensive, but high-quality evidence of efficacy and safety has been lacking. Additional evidence from two completed phase III studies is eagerly anticipated," the authors write.
Dr Hesketh reports no relevant financial relationships. Several coauthors report relationships with pharmaceutical companies, which are listed in the original article.
J Clin Oncol. Published online November 2, 2015. Full text

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