MyRisk: Efficacy and safety evaluation of oral Akynzeo® in patients receiving MEC at high risk of developing CINV based on a prediction tool. A multinational and multicenter study. Antiemetic guidelines recommendations are based on the emetogenic potential of the chemotherapy. Chemotherapy (CT) agents are divided in Highly, Moderately, Low and Minimally Emetogenic potential. In addition to type of chemotherapy, several patient-related risk factors can increase the risk of CINV (chemotherapy-induced nausea and vomiting). Currently, there is limited consensus surrounding the most relevant patient risk factors that may predict the risk of CINV. Based on a recent study by Dranitsaris et al. (Dranitsaris et al. Ann Oncol. 2017 Jun 1; 28(6):1260-1267.), eight (8) predictive factors have been identified and an algorithm has been developed to incorporate these factors into the optimal selection of prophylactic antiemetics: 1. nausea and/or vomiting in the prior cycle of chemotherapy 2. use of non-prescribed antiemetics at home in the prior cycle of chemotherapy 3. platinum or anthracycline-based chemotherapy 4. age \< 60 years 5. expectations for (anticipating) nausea and/or vomiting 6. \<7 h of sleep the night before chemotherapy 7. history of morning sickness during previous pregnancy 8. cycle of chemotherapy (A negative association between risk and number of cycles was identified where the hazard for CINV was highest in cycles 1 and 2, with a gradual decline and plateau from cycle 3 onward). The clinical application of this prediction tool has the potential to be an important resource for clinicians and may help to enhance patient care by optimizing the use of the antiemetics in a proactive manner.
Antiemetic guideline recommendations are based on the emetogenic potential of chemotherapy and involve 4 levels of classification of intravenous chemotherapy agents, i.e., high, moderate, low and minimal; these have been accepted by major organisations. Moderate emetogenic chemotherapy (MEC) results in acute vomiting in 30% to 90% of cancer patients in the absence of antiemetic therapy. In addition to the chemotherapy type, several patient-related risk factors and clinical characteristics can increase CINV risk. These can include use of antiemetics inconsistent with international guidelines, younger age, prechemotherapy nausea, no complete CINV response in an earlier cycle, history of nausea/vomiting, (trait) anxiety, fatigue experience, and expectations of nausea/vomiting. Other studies have largely confirmed some of the key risk factors for CINV (history of vomiting during pregnancy, history of motion sickness, age, gender) and added other factors such as (chronic) alcohol consumption, body surface area, fewer hours slept the night prior to infusion, or advanced stage cancer. Currently, there is a limited consensus surrounding the most relevant patient risk factors that may predict CINV risk. Based on a recent study by Dranitsaris et al. eight predictive factors have been identified, and an algorithm has been developed to combine these patient-related risk factors into the optimal treatment of prophylactic antiemetics. These include: 1. nausea and/or vomiting in the prior cycle of chemotherapy 2. use of non-prescribed antiemetics at home in the prior cycle of chemotherapy 3. platinum or anthracycline-based chemotherapy 4. age \< 60 years 5. expectations for (anticipating) nausea and/or vomiting 6. \<7 h of sleep the night before chemotherapy 7. history of morning sickness during previous pregnancy 8. cycle of chemotherapy (A negative association between risk and number of cycles was identified where the hazard for CINV was highest in cycles 1 and 2, with a gradual decline and plateau from cycle 3 onward). Akynzeo®, an oral combination of the neurokinin 1 receptor antagonists (NK1 RA), netupitant and the 5-hydroxytryptamine (HT3) receptor antagonists (5-HT3 RA), palonosetron, is recommended by guidelines for the prevention of CINV. Akynzeo® has been evaluated in a multicentre, randomised, double-blind, double-dummy phase II clinical trial at various dose ranges among 694 cisplatin-treated cancer patients from 44 sites (two countries); each NEPA (netupitant-palonosetron) dose significantly improves CINV prevention in cancer patients. Similar results were obtained in another international, randomised, double-blind and parallel group phase III clinical trial; NEPA prevented CINV in patients receiving MEC. The current study primarily aimed to evaluate whether Akynzeo® leads to a higher response rate compared with standard care in MEC regimen-treated patients who are identified to be at high risk based on the algorithm.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
414
Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle.
Standard of care will be administered on Day 1 of each cycle.
Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
Shanghai Chest Hospital
Shanghai, China
Shanghai Ninth People´s Hospital
Shanghai, China
Shanghai Obstetrics and Gynecology Hospital
Shanghai, China
Thomayerova nemocnice
Prague, Czechia
General University Hospital in Prague
Prague, Czechia
Evang. Kliniken Essen-Mitte
Essen, Germany
Universitätsmedizin Mannheim
Mannheim, Germany
München Klinik Neuperlach
München, Germany
Frauenklinik St. Louise
Paderborn, Germany
Klinikum Ernst von Bergmann gemeinnützige GmbH
Potsdam, Germany
...and 9 more locations
The Probability of Complete Responses Over Three Cycles of Chemotherapy After the Start of the MEC Administration
To evaluate if the use of NEPA (netupitant and palonosetron) in patients treated with IV moderately emetogenic chemotherapy and at high risk of CINV is more effective in preventing CINV than a standard of care antiemetics over three cycles of chemotherapy. The primary endpoint is the probability of complete responses (no emetic episode and no rescue medication), during the overall phase (0-120h), after the start of the MEC administration over three cycles of chemotherapy. This endpoint is evaluated in patients with at least one reported cycle assessment. The model-based statistics of generalized linear model were used to calculate the difference in the probability to experience a "per cycle" CINV Indicators between the treatment arms.
Time frame: At the end of all three chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Evaluation of the Probability of Acute (0 to 24 Hours), Delayed (>24 to 120 Hours), and Overall (0-120 Hours) CINV Indicators in Each Cycle of Chemotherapy
Probability of: * No emetic episode during the acute, delayed, and overall phase and daily in each cycle * No rescue medication during the acute, delayed, and overall phase and daily in each cycle * No significant nausea (maximum MAT scale = 2) during the acute, delayed, and overall phase and daily in each cycle; * No nausea (MAT scale = 0) during the acute, delayed, and overall phase and daily in each cycle; * Complete protection (no emetic episode, no rescue medication, and no significant nausea) during the acute, delayed, and overall phase and daily in each cycle Time 0 is defined as the start time of the chemotherapy administration on Day 1 of each of the three cycles. The model-based statistics of generalized linear model were used to calculate the difference in the probability to experience a "per cycle" CINV Indicators between the treatment arms.
Time frame: At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Evaluation of the Predictive Role of Potential Risk Factors in the Development of CINV Over Three Cycles of Chemotherapy
Analysis of the development of CINV as a dependent variable will be performed to identify additional potential risk factors of CINV thought to be increasing the risk of CINV in patients receiving MEC. The outcome measure is the development of CINV, defined as any occurrence of nausea or a vomiting episode. The data on the development of CINV will be taken from data collection tools, patients' diaries and MASCC Antiemesis Tool (MAT).
Time frame: At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Evaluation of the Safety Profile of the Antiemetic Drug Over Three Cycles of Chemotherapy - the Frequency of Adverse Events (AE)
An overall summary of adverse events (AE) will be presented, including the frequency of patients with: * Any treatment-emergent adverse event * Any treatment-emergent adverse event related to a study drug * Any treatment-emergent adverse event leading to chemotherapy dose reductions or interruptions * Any treatment-emergent serious adverse event All AEs will be summarized by their: * Severity * Seriousness * Relationship to a drug
Time frame: At the end of all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Evaluation of the Safety Profile of the Antiemetic Drug Over Three Cycles of Chemotherapy - Percentage of Participants With Adverse Events
An overall summary of adverse events (AE) will be presented, including the percentage of patients with: * Any treatment-emergent adverse event * Any treatment-emergent adverse event related to a study drug * Any treatment-emergent adverse event leading to chemotherapy dose reductions or interruptions * Any treatment-emergent serious adverse event All AEs will be summarized by their: * Severity * Seriousness * Relationship to a drug
Time frame: At the end of all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Number of Participants With Discontinuations Due to Adverse Events
The frequency of discontinuations due to adverse events (AE) will be presented.
Time frame: At the end of all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Percentage of Participants With Discontinuations Due to Adverse Events
The percentage of patients with discontinuations due to adverse events (AE) will be presented.
Time frame: At the end of all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Number of Participants With Death Due to Adverse Events
The frequency of on treatment deaths due to adverse events (AE) will be presented.
Time frame: At the end of all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Percentage of Participants With Death Due to Adverse Events
The percentage of patients with on treatment death due to adverse events (AE) will be presented. All AEs leading to on treatment death will be summarized by their: * Severity * Seriousness * Relationship to a drug
Time frame: At the end of all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Exploration of the Effect of CINV on Daily Activities and Quality of Life in Patients Receiving Moderately-emetogenic Chemotherapy Over Three Cycles of Chemotherapy
Evaluation of the effect of CINV on daily activities and quality of life that will be measured by using the Functional Living Index-Emesis (FLIE) questionnaire, a validated, nausea and vomiting specific, patient-reported outcome instrument. The Functional Living Index-Emesis (FLIE) has 18 questions. These questions are divided into two domains: Nausea (questions 1-9) and Vomiting (questions 10-18). The minimum score for any question is 0 and the maximum score is 100. Higher scores indicate less impairment on daily life as a result of nausea or vomiting. The model-based statistics of generalized linear model were used to calculate the difference in the score "per cycle" between the treatment arms.
Time frame: At the end of chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Evaluation of Resource Utilization and Health Economic Outcome - Number of Days With Rescue Medication Administered for the Treatment of CINV
Health economic endpoint, the number of days with rescue medication administered for the treatment of CINV, will be evaluated during the study cycles
Time frame: At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Evaluation of Resource Utilization and Health Economic Outcome - Daily Doses of Rescue Medication Administered for the Treatment of CINV
Health economic endpoint, the daily doses of rescue medication administered for the treatment of CINV, will be evaluated during the study cycles
Time frame: At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Evaluation of Resource Utilization and Health Economic Outcome - the Number of Re-hydration Bags
Health economic endpoint, the number of re-hydration bags given for at least grade 2 vomiting (more details below), will be evaluated during the study cycles
Time frame: At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Evaluation of Resource Utilization and Health Economic Outcome - the Number of Days of Unplanned Hospitalisations
Health economic endpoint, the number of days of unplanned hospitalizations related to CINV, will be evaluated during the study cycles All hospitalizations will be summarized according to the department of hospitalization (type of ward)
Time frame: At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Evaluation of Resource Utilization and Health Economic Outcome - the Number of Outpatient Physician Visits
Health economic endpoint, the number of outpatient physician visits and health care consultations due to CINV (e.g., general practitioner), will be evaluated during the study cycles
Time frame: At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Evaluation of Resource Utilization and Health Economic Outcome - the Number of Unplanned Laboratory Test
Health economic endpoint, the number of unplanned laboratory test including those at unplanned hospitalizations due to CINV, will be evaluated during the study cycles
Time frame: At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Evaluation of Resource Utilization and Health Economic Outcome - Discontinuation of Chemotherapy Treatment Due to CINV
Health economic endpoint, the number of discontinuations of chemotherapy treatment due to CINV, will be evaluated during the study cycles
Time frame: At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Evaluation of Resource Utilization and Health Economic Outcome - the Number of Delays of Chemotherapy Administration Due to CINV
Health economic endpoint, the number of delays of chemotherapy administration due to CINV, will be evaluated during the study cycles. Delays will be observed after the first administration of Cycle 1 for Cycles 2 and 3.
Time frame: At the start of cycles 2 and 3. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Evaluation of Resource Utilization and Health Economic Outcome - the Average Length of Delay of Chemotherapy Administration Due to CINV
Health economic endpoint, the average length of delay (in days) of chemotherapy administration due to CINV, will be evaluated during the study cycles. Delays will be observed after the first administration of Cycle 1 for Cycles 2 and 3.
Time frame: At the start of Cycles 2 and 3. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Evaluation of Resource Utilization and Health Economic Outcome - Days of Absence From Work
Health economic endpoint, the number of days of absence from work, will be evaluated during the study cycles
Time frame: At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
Evaluation of Acute (0 to 24 Hours), Delayed (>24 to 120 Hours), and Overall (0-120 Hours) CINV Indicators in Each Cycle of Chemotherapy
Number of vomiting episodes during the acute, delayed, and overall phase in each cycle Time 0 is defined as the start time of the chemotherapy administration on Day 1 of each of the three cycles. The model-based statistics of generalized linear model were used to calculate the difference in the number of vomiting episodes "per cycle" between the treatment arms.
Time frame: At the end of chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).
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