Oncologist perspectives on chemotherapy‐induced nausea and vomiting (CINV) management and outcomes: A quantitative market research‐based survey

Abstract Background Chemotherapy‐induced nausea and vomiting (CINV) is a distressing side effect that can negatively impact patients' quality of life and could discourage completion of chemotherapy, thereby affecting overall treatment outcomes. Although adherence to antiemetic guidelines can reduce CINV incidence in patients receiving highly or moderately emetogenic chemotherapy, CINV control remains inadequate. Aims The objectives of this survey were to determine oncologists' practice patterns in CINV management, identify factors that contribute to antiemetic treatment failure, and determine the outcomes of uncontrolled CINV on health care resource utilisation and on patients' attitude towards chemotherapy. Methods and results Quantitative market research was performed using an online questionnaire. Responses from 300 European oncologists who prescribe antiemetics and see ≥50 patients/month were analysed. Results showed that the main reasons reported by oncologists for antiemetic treatment failure were underestimating the emetogenic potential of chemotherapy, utilising weaker antiemetic regimens than required, and patient non‐adherence because of administration mistakes or missed/delayed doses. Educational initiatives for the oncology multidisciplinary team may help improve guideline‐consistent prescribing. Also, the availability of simpler, more convenient antiemetic therapies may improve guideline adherence and patient compliance during home administration. Conclusion Achieving effective CINV control is a crucial goal to improve patients' quality of life, which should optimise chemotherapy outcomes, and would ultimately reduce health care costs.

recent study, a direct correlation between the use of antiemetics and chemotherapy treatment compliance was demonstrated, where the use of the 5-hydroxytryptamine-3 receptor antagonist (5-HT 3 RA) palonosetron was shown to improve adherence to highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. 3  Effective prevention of CINV in the first 24 hours after chemotherapy (acute CINV) is critical to reduce its incidence in subsequent days (days 2-5, delayed CINV). 7 Additionally, it has been shown that effective CINV control during cycle 1 of chemotherapy is important to reduce the risk of CINV in subsequent cycles, and to reduce anticipatory nausea, a challenging symptom that involves anxiety and psychological factors relating to previous experience of CINV. 8,9 These studies demonstrate that early control of CINV is vital for optimal CINV management throughout the entire chemotherapy schedule. However, despite advances in antiemetic therapy, a significant proportion of patients receiving chemotherapy outside of randomised clinical trials still suffer from nausea and vomiting, which may indicate suboptimal use of evidence-based antiemetic therapy guidelines in clinical practice. 3,10,11 In fact, while guideline-consistent antiemetic therapy has been shown to improve CINV control in cancer patients, there appear to be barriers to the use of these guidelines by health care professionals. [10][11][12] Low adherence to use of antiemetics by patients at home may also contribute to the suboptimal management of CINV, since poor compliance to treatment is fairly common in many diseases and correlates with poorer outcomes and increased health care costs. The reasons for low adherence are often complex and include patient characteristics as well as the nature of the treatment regimen. 13 The growing use of oral chemotherapy and supportive medications administered at home increases the potential for non-adherence by patients, with multiple consequences, including unnecessary therapy adjustments because of a perceived lack of response, increased health care costs, and increased toxicities if the medication is not taken as prescribed. 13 Hence, the effectiveness of antiemetic therapy in preventing CINV relies on the efficacy of antiemetic agents, physicians prescribing in accordance with treatment guidelines, and patients adhering to the treatment regimen. Identifying the barriers to utilising guideline-recommended antiemetics in clinical practice may help design more-convenient antiemetic regimens that increase treatment adherence and ultimately improve clinical outcomes.
The objectives of this quantitative market research-based survey were to determine oncologists' practice patterns in CINV management, identify factors that might contribute to antiemetic treatment failure, determine the outcomes of uncontrolled CINV on the use of health care resources, identify whether oncologists detect changes in the attitude of their patients towards the planned chemotherapy after experiencing CINV, and to recognise the consequences of noncompliance with antiemetic guideline recommendations in the prescription patterns of oncologists.

| Survey design and inclusion criteria
Quantitative market research based on an online survey was performed in May 2012. The questionnaire was designed by Genactis Italy Srl and medical specialists at Helsinn Healthcare, and based on current literature and antiemetic guidelines at the time of study conduct. The survey setup and raw data collection were performed using a platform written in C#/.net, which integrates a MS-SQL database, and is run over a secured multitier Web architecture. The questionnaire was programmed using the Questionnaire Markup Language, a high-level semantic XML language. The 11 questions included in the survey are listed in Table 1.
Survey participants met the following criteria: lived in Italy, France, Germany, Spain, or the UK; were registered oncologists; were common prescribers of antiemetic therapies; and at the time of the survey treated an average of at least 50 cancer patients per month.
Potential participants were sent an email invitation that contained a direct link to the Web site hosting the survey. Upon accessing the Web site, participants were provided with a short description of the study and were asked to accept a confidentiality agreement before entering the survey. Participants then answered a screening question regarding the average number of cancer patients they see in a month (for all); participants from Germany were also asked to indicate their type of practice (office/private practice or hospital practice) and were eligible to participate up until meeting a final allocation target of 50% in office practice and 50% in hospital practice. Only respondents who met the eligibility criteria and passed the screening were allowed to proceed to the survey, which was estimated to be completed in approximately 20 minutes.
Participants were blinded to the study sponsor. Responses were based on oncologists' perceptions at the time of survey completion and did not involve the review of patients' files. Individual patient data were not collected; therefore, institutional review board assessment was not required.

| Statistical analyses
Data from the survey were summarised by descriptive statistics. The frequencies (percentage) were calculated where applicable. The • actual emetogenicity higher than expected • "weaker" antiemetics (eg, monotherapy instead of combination) were used • mistakes/issues with the administration (ie, time of administration, etc) • other: Mainly psychological cofactors, anxiety, individual sensitivity 8. Considering all your patients treated with antiemetic therapies for whom you prescribe treatments to take at home, what percentage of these patients made mistakes/missed one or more administrations?
Please indicate the percentage of patients 9. What percentage of your patients who receive chemotherapy treatment or target therapy undergo additional medical visits or require additional therapy (eg, you had to undertake an unplanned visit and/ or prescribe a rescue antiemetic treatment) for emesis-related reasons after receiving their cycle of chemotherapy?

10.
To what extent do you perceive unplanned visits and/or changes in planned antiemetic treatment due to emesis problems in treated patients as an issue in your personal clinical practice? Please answer using a 1 to 7 scale, where 1 = it is not at all an issue and 7 = it is a major issue.
compiled data collected from participants from the five European countries are presented (n = 299). In addition, the perceived frequency of non-adherence to treatment during home administration of antiemetics is shown for the individual countries.
For the analysis of responses to survey question 4, the percentages of patients in therapy options b and c were combined in the "5-HT 3 RA +/-steroids" group, the percentages of patients in therapy options d and e were combined in the "NK 1 RA +/-steroids" group, and the percentages of patients in therapy options f, g, and h were combined in the "5-HT 3 RA + NK 1 RA +/-steroids" group.
In the analysis of responses, scores were grouped into the following predetermined categories • Minor/no issue (scores 1-3 of a 1-7 scale, where 1 = it is not at all an issue and 7 = it is a major issue); • Moderate/major issue (scores 5-7 of a 1-7 scale, where 1 = it is not at all an issue and 7 = it is a major issue); • Low/no agreement (scores 1-3 of a 1-7 scale, where 1 = disagree completely and 7 = agree completely); • Moderate/high agreement (scores 5-7 of a 1-7 scale, where 1 = disagree completely and 7 = agree completely.

| Survey participants
One thousand four hundred fifty-five oncologists were invited to participate in the survey, of whom a total of 299 responded and completed the survey (1141 oncologists did not access or did not complete the questionnaire, and 15 oncologists were screened out).
Overall, 60 oncologists each from Italy, France, Germany, and Spain, and 59 oncologists from the UK participated in the survey. All of the respondents from France, Italy, Spain, and the UK were hospital oncologists. Amongst the German participants, 50% were hospital oncologists and 50% were office-based oncologists. Responses from participating oncologists were combined and are presented in

| Degree of awareness and adherence to international antiemetic guidelines
Amongst the participating oncologists, awareness of the ASCO antiemetic guidelines was highest, followed by the NCCN and MASCC/ ESMO guidelines ( Figure 1A).
Overall, a moderate to high degree of adherence to guidelines was reported ( Figure 1B

11.
To what extent do you perceive hospitalisation due to emesis as an issue in your personal clinical practice. Please answer using a 1 to 7 scale where 1 = it is not at all an issue and 7 = it is a major issue.
12. To what extent do you perceive patient adherence/compliance to antiemetic treatments as an issue in your personal clinical practice? Please answer using a 1 to 7 scale, where 1 = it is not at all an issue and 7 = it is a major issue.
13. Please indicate how much you agree with the list of statements below, indicating 7 for agree completely and 1 for disagree completely.
A. I sometimes avoid or reduce highly emetogenic chemotherapy for some patients because of chemotherapy-induced nausea and vomiting B. Patients sometimes ask to change or cancel chemotherapy because they experienced emesis on previous courses of therapy C. An antiemetic drug administered orally even on day 1 would be much appreciated by me and my patients • 5 In general, the emetogenic potential of chemotherapy was underestimated, with 11%, 83%, and 21% of oncologists perceiving cisplatin (>50 mg/m 2 ), cisplatin (<50 mg/m 2 ), and cyclophosphamide (>1500 mg/m 2 ), respectively, as mildly or moderately emetogenic.
One third of respondents considered anthracycline-cyclophosphamide regimens (currently classified as HEC) to be moderately emetogenic ( Figure 2B).

| Perceived incidence of CINV and types of symptoms with current antiemetic therapies
Despite antiemetic prophylaxis, respondents reported an incidence of CINV of 15% (acute phase) and 18% (delayed phase) in their patients receiving MEC, and 21% (acute phase) and 26% (delayed phase) in patients receiving HEC ( Figure 3A). Of those patients experiencing CINV, oncologists reported that most patients experience nausea only (58%), approximately a third of patients experience both nausea and vomiting (29%), and 13% of patients experience vomiting only ( Figure 3B).

| Potential reasons for antiemetic treatment failure
The estimated proportions of patients experiencing CINV because of antiemetic treatment failure for various reasons are shown in Figure 4A. The main reason cited for treatment failure during the acute and delayed phases was that actual chemotherapy emetogenicity was higher than expected (43% and 39% for acute and delayed CINV, respectively). The second most important reason cited by the survey participants was the use of "weaker" antiemetic regimens than required, such as use of monotherapy instead of combinations, which results in emesis in approximately a third of patients during both the acute and delayed phases (31% and 33%, respectively). An additional concern for oncologists was errors during the administration of antiemetics, including mistakes or issues with administration, which were perceived as a reason for treatment failure affecting more patients in the delayed phase (21% vs 17% in the acute phase). Oncologists from all European countries consistently reported that during home administration of antiemetics, approximately a third of patients (range: 30%-39%) made administration mistakes or missed/delayed one or more doses ( Figure 4B). This non-adherence to antiemetic treatment by patients was perceived as a moderate/major issue by nearly half of oncologists (42%) (Figure 5 B). The potential benefit of antiemetic therapy simplification as a means to improve CINV control was explored, and most oncologists (69%) thought that an antiemetic drug administered orally on day 1 would be appreciated in their clinical practice and by their patients ( Figure 4C).

| Potential consequences of antiemetic treatment failure
A total of 35% and 14% of oncologists considered that >10% of patients undergo additional medical visits or require additional antiemetic therapy for CINV-related reasons after HEC and MEC, respectively ( Figure 5A). Approximately one-third of respondents (33%) perceived this need for additional visits or for rescue antiemetic therapies as an issue of moderate to major concern ( Figure 5B). Similarly, one-third of respondents (31%) perceived hospitalisation because of emesis as an important issue ( Figure 5B). The failure of antiemetic treatment led to changes in attitude towards the design of the antiemetic regimen for physicians, and towards the planned chemotherapy treatment for patients ( Figure 5C), with approximately a third of oncologists (29%) reporting that they agreed that they sometimes avoid or reduce HEC for some patients because of CINV. A total of 42% of oncologists agreed that patients sometimes ask to change or cancel chemotherapy because of previous CINV episodes. However, the reported prescription patterns (Figure 2A) showed suboptimal adherence to guidelines, which is in line with observations in more-recent studies. 10,11,[14][15][16] In addition, recent surveys assessing perceptions and practice patterns amongst oncology nurses in the US 12 and Europe 17 revealed that, from the nurses' perspective, physician preference is the main barrier to guideline-recommended prescription of antiemetic prophylaxis. 14 Consistent with the results from the present survey, various studies have shown that the incidence of CINV is often underestimated by medical oncologists and oncology nurses, 18  can provide valuable assistance with the evaluation of patient-related risk factors when making treatment decisions. Integration of the patient's personal risk factors will allow for more efficient control of nausea and vomiting and optimise antiemetic use. 16 In addition, reevaluation of chemotherapeutic agents and/or regimens in specific patient populations may be of value in uncovering the need for a triplet antiemetic combination in particular settings.
Non-adherence during home administration of antiemetics was identified as an issue in approximately one-third of patients, which supports the results of the recent surveys of oncology nurses, where patients' non-adherence to treatment was ranked amongst the top challenges in managing CINV. 12,17 Non-adherence can lead to worse outcomes of chemotherapy, as reported in patients with breast cancer receiving anthracycline-based chemotherapy. 25 While there can be multiple reasons for non-adherence to antiemetic therapy, patient characteristics, regimen complexity, and education about antiemetics are important factors. Additionally, in a recent study, some patients specified that they waited until they felt nauseated before taking the medication, failing to understand that antiemetics are taken for the prophylaxis of CINV. 18 Therefore, numerous strategies that involve a multidisciplinary team of health care professionals and include active educational initiatives, as well as highlighting the importance of patient