The EPIC Study

Official Title

A Randomized, Phase III Trial of Individualised Care versus Standard Care, in the Prevention of Chemotherapy Induced Nausea and Vomiting in Breast Cancer Patients.

Summary:

Despite widespread anti-emetic use nausea and vomiting remain among the most feared and expected side effects of chemotherapy. Inadequately controlled nausea and vomiting impairs functional activity and quality of life for patients, increases the use of health care resources, and may occasionally compromise treatment adherence.
 
Given the importance of emesis control and in an attempt to individualize patients’ anti-emetic regimen, we have designed a study that will use the mathematical decision aid (emesis risk calculator) in the setting of patients at high-risk of emesis (i.e. BOTH nausea and vomiting) to see if we can optimize individual patient management. Since most adjuvant breast cancer patients still receive an anthracycline with cyclophospamide-based chemotherapy, if standard anti-emetic guidelines are followed then the majority of them should in theory receive aprepitant (an NK-1 antagonist). The emesis risk calculator could therefore be used to determine if all high-risk patients would require a NK-1 inhibitor (as per the treatment guidelines) or not.
In addition, anti-emetic use in clinical practice is hugely variable. Some physicians recommend treating all patients, regardless of their Hesketh score, with NK-1 antagonists in order to “guarantee” anti-emetic control. Others recommend treating no one with an NK-1 antagonist except a select few that have a very high Hesketh score (e.g. patients receiving platinum). We propose that individualization of the use of NK-1 inhibitors would be the ideal practice and this can be achieved by using the emesis risk calculator. The benefits are not only that complete emetic control will be achieved with the minimum required anti-emetics but that we will have a tool to selectively identify which patients would or would not benefit from NK-1 antagonists. This is vital information not only for patients and physicians but as well for Provincial regulatory bodies.

Trial Description

Primary endpoint:

• Incidence of complete prevention of acute emesis (nausea and/or vomiting) in both study arms

Secondary endpoints:

• Incidence of complete prevention of delayed emesis (nausea and/or vomiting) in both study arms
• If emesis is not prevented during the first cycle, the rate of emesis control during cycle 2.
• Incidence of acute or delayed nausea and vomiting less than NCIC-CTC grade 2/3 in both study arms
• Difference in breakthrough anti-emetic use in the emesis risk model group compared to the standard arm; i.e.: requirements for additional oral and parenteral anti-emetics during a single chemotherapy cycle
• Patient-Reported Impact on Daily Life:
  • The FLIE questionnaire is a validated patient-reported measure of the impact of chemotherapy induced emesis on daily life. It is a short, self administered instrument containing two domains—one for nausea (9 items) and one for vomiting (9 items). The questionnaire will be administered before the initiation of chemotherapy and on days 1 and 6.

Patients with newly diagnosed breast cancer who are about to start an anthracycline and cyclophosphamide-based chemotherapy regimen (e.g. FEC or AC) will be approached by a member of their health care team (. If the patient consents to the study and is eligible for the study she will then be randomized to either receive:

• Standard anti-emetics based on her oncologists’ choice
• Anti-emetics based on her personal emesis risk using the mathematical decision aid (emesis risk calculator).

In the standard anti-emetic arm, the treating medical oncologist will determine the choice of anti-emetic regimen that they perceive the patient would require and prescribe it. The treating physician will be blinded to result of the personalized composite emesis score in order to not bias the study.
 
In the emesis risk model arm, an emesis risk score will be calculated for both acute and delayed emesis prior to the start of intravenous chemotherapy using the emesis risk calculator. The anti-emetic prophylaxis treatment will follow the emesis risk score table. Whereby either an acute emesis score of ≥7 and/or a delayed emesis score of >16 will be considered high-risk. The anti-emetics will be prescribed reflecting this risk and for this study we are using the Cancer Care Ontario Guideline. For subsequent cycles the anti-emetic score will be re-calculated prior to each cycle and the choice of anti-emetics adjusted if necessary.

In the event that the patient experienced CINV, in the standard anti-emetic arm, modifications to the initial anti emetic regimen would be left to the treating physician's discretion whereas in the experimental arm (using the emesis risk calculator), the next level of anti-emetic therapy following a dose escalation table will be given prior to the next cycle of chemotherapy.

Risk factors for both acute and delayed emesis will be determined for each patient prior to treatment. Anti-emetic control will be determined by patient diaries that will record the intensity and frequency of nausea and vomiting episodes, effect of CINV on daily life and use of non-prescription anti-emetics after chemotherapy treatment.

We predict that in breast cancer patients receiving adjuvant anthracycline and cyclophosphamide-based chemotherapy regimens, the use of a validated emesis risk calculator will provide superior anti-emetic control compared with the “standard” anti-emetic regimen.