The impact of 5-hydroxytryptamine-receptor antagonists on chemotherapy treatment adherence, treatment delay, and nausea and vomiting

Purpose: To determine the incidence of chemotherapy-induced nausea/vomiting (CINV) and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT₃ RA) antiemetics.
Materials and methods: This retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame.
Results: We identified 1,832 palonosetron and 2,387 other 5-HT₃ RA (“other”) patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026), and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, P<0.0001; MEC, 17.0% versus 26.8%, P<0.0001). Compared with the other cohort, patients receiving palonosetron were significantly more adherent to the index chemotherapy regimen with respect to the recommended time frame (HEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%,P=0.0019) and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%,P=0.0019).
Conclusion: Palonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with other agents in this real-world setting. Additionally, patients receiving palonosetron had better adherence and fewer treatment delays than patients receiving other 5-HT₃RAs.

Keywords: palonosetron, adherence, CINV, delay of therapy, observational, health services research

Nausea and vomiting are common chemotherapy-associated side effects ranked by patients as especially distressing.^1–7 Chemotherapy-induced nausea and vomiting (CINV) can cause psychological distress, nutritional deficiencies, and reduced quality of life among patients receiving chemotherapy.^5–8 Furthermore, its occurrence may potentially affect adherence to chemotherapy regimens, leading to treatment delays or receipt of fewer treatments or lower dosages than recommended.^9,10 Such events may have an adverse effect on treatment efficacy, ultimately resulting in suboptimal clinical outcomes and potentially increased health care-related resource utilization and costs.³

Recognizing the importance of preventing and managing CINV, leading oncology societies have issued treatment guidelines^11–13,29 recommending 5-hydroxytryptamine-receptor antagonists (5-HT₃ RAs) as the preferred medication class to effectively prevent CINV in patients receiving highly emetogenic chemotherapy (HEC) or moderately EC (MEC).^19,20 Compared to the older agents, palonosetron – a newer 5-HT₃ RA – is pharmacologically distinct, with a longer half-life and greater receptor-binding affinity, allosteric binding to serotonin receptors with positive cooperativity, and cross talk with Neurokinin-1 (NK-1) receptors.^21–23 While the early 5-HT₃ RA compounds were considered equally efficacious,¹⁹ palonosetron demonstrated greater efficacy than active comparators in preventing CINV in patients receiving HEC or MEC in multiple clinical trials.^20,24–26 Hatoum et al compared palonosetron with other 5-HT₃ RAs in a real-world setting among patients with breast/lung cancer undergoing cisplatin/carboplatin treatments.^19,27 They concluded that patients who received prophylaxis with palonosetron had a significantly lower risk of CINV events than those who had received other 5-HT₃RA agents. Furthermore, those breast/lung cancer patients receiving palonosetron experienced 49.5% and 29.1% fewer CINV days, respectively.²⁷ Their study focused on serious CINV events resulting in hospital or emergency department admissions, and did not include CINV events occurring in an outpatient context. Craver et al found that prophylactic administration of palonosetron among patients with hematologic malignancies who were receiving HEC/MEC resulted in a 20.4% decrease in CINV event rate per cycle compared with patients receiving other 5-HT₃ RAs.²⁸ However, while 5-HT₃RA agents have been proven effective in preventing CINV, little is known regarding their impact on chemotherapy treatment adherence and delay. To address these questions, a real-world study was designed comparing patients who received palonosetron with those who received other 5-HT₃ RAs on incidence of acute and delayed CINV and chemotherapy treatment delay and adherence. This study also contributes to the development of methods to assess medication adherence for intravenous (IV) agents.