Practice Patterns for Prevention of Chemotherapy-Induced Nausea and Vomiting and Antiemetic Guideline Adherence Based on Real-World Prescribing Data

Abstract

Background. Guideline-recommended antiemetic prophylaxis improves nausea and vomiting control in most patients undergoing chemotherapy. Multinational Association of Supportive Care in Cancer/European Society for Medical Oncology (MASCC/ESMO) antiemetic guidelines recommend prophylaxis with a neurokinin-1 receptor antagonist (NK 1 RA), a 5-hydroxytryptamine-3 (5-HT 3)RA, and dexamethasone for patients receiving highly emetogenic chemotherapy (HEC), including anthracycline-cyclophosphamide (AC)-and carboplatin (considered moderately emetogenic chemotherapy)-based chemotherapy. Here, we analyze the use of NK 1 RA-5-HT 3 RA-dexamethasone for antiemetic prophylaxis associated with HEC and carboplatin. Methods. The data source was the Global Oncology Monitor (Ipsos Healthcare). Geographically representative physicians from France, Germany, Italy, Spain, and UK were screened for treatment involvement and number of patients treated/month. Patients' data from Jan-Dec 2018 were collected from medical charts and extrapolated on the basis of the total number of physicians who prescribe chemotherapy. The emetic risk of chemotherapy was classified per MASCC/ESMO guidelines. Results. Data from 45,324 chemotherapy-treated patients were collected, representing a total extrapolated prevalence of 1,394,848 chemotherapy treatments included in the analysis. NK 1 RAs were used in 45%/42%/19% of patients receiving cisplatin-/AC-/carboplatin-based chemotherapy, respectively; 18%/24%/7% received the guidelinerecommended NK 1 RA-5-HT 3 RA-dexamethasone combination; no antiemetics were prescribed for 12% of the treatments. Often, physicians' perception of the emetic risk of chemotherapy did not follow MASCC/ESMO guideline classification. Conclusion. Low adherence to antiemetic guidelines was revealed in clinical practice in five European countries, with 15% of all HEC-/carboplatin-based treatments receiving guideline-recommended NK 1 RA-5-HT 3 RA-dexamethasone prophylaxis, and 12% of them receiving no antiemetics. New strategies for improving guideline adherence are urgently needed. The Oncologist 2021;9999:• • Implications for Practice: Despite recent advances in antiemetic therapy, a substantial proportion of patients experience nausea and vomiting associated with chemotherapy in daily clinical practice. Antiemetic guidelines aim at prevention of chemotherapy-induced nausea and vomiting (CINV) and guideline-consistent antiemetic therapy can effectively prevent vomiting and, to a lesser extent, nausea in most patients with cancer. This study reports low adherence to antiemetic guidelines in the highly emetogenic chemotherapy setting in daily clinical practice across five European countries. Opportunity

Mechanisms of Nausea and Vomiting: Current Knowledge and Recent Advances in Intracellular Emetic Signaling Systems

“…Being an ion channel, 5-HT 3 receptor activation induces fast excitatory postsynaptic potentials and rapid depolarization of serotonergic neurons [ 48 ], leading to augmentation of intracellular Ca 2+ concentration that causes the release of different emetic neurotransmitters and/or peptides (e.g., dopamine, cholecystokinin, glutamate, acetylcholine, substance P, or 5-HT, itself [ 49 ]. Significant clinical evidence indicates that both the first (e.g., ondansetron, Granisetron, dolasetron) and second (e.g., palonosetron) generation 5-HT 3 receptor antagonists attenuate the first phase of cancer chemotherapy-evoked vomiting where serotonin is a major emetic player [ 50 , 51 ]. In fact, combination of a 5-HT 3 receptor antagonist with a substance P neurokinin NK 1 receptor antagonist plus dexamethasone is required to prevent both phases of highly emetogenic chemotherapy-evoked vomiting in approximately 90% of cancer patients.…”

“…In fact, combination of a 5-HT 3 receptor antagonist with a substance P neurokinin NK 1 receptor antagonist plus dexamethasone is required to prevent both phases of highly emetogenic chemotherapy-evoked vomiting in approximately 90% of cancer patients. Although 5-HT 3 receptor antagonists are generally considered as narrow-spectrum antiemetics, they are also useful for the suppression of postoperative nausea and vomiting, as well as pregnancy-induced emesis [ 50 , 51 , 52 ].…”

“…In the clinic, NK 1 R antagonists (such as Aprepitant, netupitant and rolapitant) are recommended for the suppression of the second phase of vomiting evoked by highly emetogenic cancer chemotherapeutics [ 59 ]. In fact, they are one major component of the so-called “triple prophylactic antiemetic therapy”, along with one of the above-described 5-HT 3 receptor antagonists plus dexamethasone [ 50 , 51 , 52 , 60 ]. Basic studies have indicated that NK 1 R antagonists behave as broad-spectrum antiemetic [ 61 ] and are also effective against postoperative nausea and vomiting in the clinic [ 62 , 63 ]; however, they are not recommended in patients on birth control medications, since aprepitant reduces the effectiveness of oral contraceptives [ 59 ].…”

“…Prevention: Various antiemetic guidelines have been developed for the prophylactic treatment of chemotherapy- and radiotherapy-induced nausea and emesis [ 50 , 51 , 52 , 60 ]. As discussed earlier, while the triple antiemetic therapy (a 5-HT 3 receptor antagonist with an NK 1 receptor antagonist plus the corticosteroid dexamethasone) has revolutionized prophylactic antiemetic therapy against both the acute and delayed phases of vomiting caused by highly emetogenic chemotherapeutic regimens, neither complete emesis protection in all cancer patients, nor significant nausea protection has yet been achieved [ 155 , 156 ].…”

Implementation Strategies to Support Evidence-Informed Symptom Management Among Outpatient Oncology Nurses: A Scoping Review Protocol

“…20 Despite increasing awareness and availability of SMG over the last decade, interdisciplinary cancer care providers do not consistently utilize these guidelines in practice, citing barriers such as lack of knowledge, time, buy-in, resources, and enforcement. 21 22 Recent empirical evidence suggests SMG adherence remains low; for example, it is estimated that oncologists provide recommended antiemetic prescriptions to only 15% of European patients, 23 and only 33% of outpatient oncology nurses in one Canadian setting were found to document symptom management according to established guidelines. 24 Subsequently, cancer-related symptoms are often unmanaged.…”