Real-world effectiveness of palonosetron-based antiemetic regimens: preventing chemotherapy-induced nausea and vomiting

This was a retrospective longitudinal database analysis of third-party payer claims containing longitudinal medical (outpatient and inpatient) and pharmacy claims data, including patients covered by employer-sponsored and government insurance programs (Medicare, Medicare Advantage and Medicaid). Selected patients were aged 18 years or older with a diagnosis of any solid tumor (presence of at least one nondiagnostic medical claim with an International Classification of Diseases, Ninth Revision [ICD-9] code of 140–151.x, 153.x, 156–157.x, 159.xx, 162.x, 164.x, 170.x, 172.x, 174–176.x, 179, 180–189.x, 193 or 195.x) and had initiated first-line treatment with a HEC regimen (anthracycline ± cyclophosphamide, or cisplatin) or carboplatin between 1 January 2012 and 31 December 2014. The data cutoff was 31 December 2015. Patients were required to have completed first-line chemotherapy, as evidenced by a discontinuation of therapy (gap of >90 days), or to have switched to a subsequent treatment regimen. Cycles were approximated based on the dates of claims for the infusion of chemotherapy. Patients must have been treated with a three-drug antiemetic regimen comprising palonosetron – an NK-1 RA – and dexamethasone if they had received HEC, and with a palonosetron-containing antiemetic regimen if they had received carboplatin; they also must have had data available for the full first line of therapy treatment period, including time for claims maturation. All claims had been fully adjudicated by the time of data access. Patients were excluded if they had been participating in any interventional clinical trial, received benzodiazepines within 7 days of starting chemotherapy and antiemetics, received radiation therapy -7 to +6 days from the first day of the chemotherapy cycle, or if records were not available in the database for 1 month prior to the first dose of chemotherapy. As the research involved the de-identified Health Insurance Portability and Accountability Act of 1996 (HIPAA)-compliant database, no institutional review board approval was necessary.

The objectives of the study were to assess the following over cycle 1 and across all cycles of the selected HEC and MEC regimens by patient and by patient cycle: nausea and vomiting events, HCRU, rescue medication use, changes in prophylactic antiemetic regimens and antiemetic efficacy. In addition, the study compared differences in these parameters between patients receiving HEC and MEC.

Nausea and vomiting events were recorded at any time during each chemotherapy cycle, regardless of whether they occurred during the acute or delayed phase of CINV. Events were assessed by ICD-9 codes [25]. Data were included in the analysis if the ICD-9 codes used in the claims database were consistent with symptoms or outcomes related to CINV, as assessed by the treating physician (Table 1). Any code or combination of codes occurring on chemotherapy cycle day 1 was considered one event; if a code was identified on a subsequent day, that was defined as a separate CINV event. ICD-9 codes were used, as they designate the diagnosis for which a service was performed (whereas Current Procedural Technology [CPT] codes indicate a claim for a service provided). Thus, nausea and vomiting events were defined using diagnoses only, so as not to identify services that might have been delivered for other diagnoses (e.g., a hydration service administered for diarrhea).

The duration of the first line of therapy was measured as the time from the start of the first line of therapy until the start of the second line of therapy. The time to discontinuation of the first line of therapy was measured as the time from the start of the first line of therapy to the last injection date for the first line of therapy prior to the patient receiving the next line of therapy.

HCRU associated with CINV events was determined by the numbers of all-cause (scheduled or unscheduled) and CINV-related physician clinic visits, ER visits and hospitalizations by cycle for cycle 1 and across all cycles.

Scheduled prophylactic antiemetic regimen changes (i.e., deliberate changes to a prophylactic antiemetic regimen to be administered) were determined by cycle for cycle 1 and across all cycles. Rescue medication use (i.e., addition of an unscheduled antiemetic), calculated from day 2 of chemotherapy onward by cycle for cycle 1 and across all cycles, was assessed by a claim for any antiemetic drug not already prescribed from the date after chemotherapy treatment to the end of the CINV episode during each chemotherapy cycle.

Antiemetic efficacy was determined by the absence of a CINV event over cycle 1 and across all cycles. A CINV event was defined as any event listed in the ICD-9 codes (e.g., nausea, vomiting or dehydration), and the administration of an unscheduled iv. antiemetic. An unscheduled iv. antiemetic was defined as any antiemetic that was not prescribed prior to chemotherapy and that started on chemotherapy day 2 or later.

Data were collected and analyzed for the duration of the first-line chemotherapy regimen. Other collected data included follow-up time from diagnosis, duration of first-line chemotherapy, time from start of first-line chemotherapy to discontinuation, time from diagnosis to first-line chemotherapy discontinuation and number of chemotherapy treatment cycles. The duration of chemotherapy was defined as day 1 of each chemotherapy cycle to day -1 of the next cycle. Assessments were done for all cycles and for cycle 1 only.

Patient baseline demographics and treatment characteristics were analyzed using descriptive statistics. Categorical variables were tabulated as frequency and percentage. Continuous variables were calculated as mean (standard deviation [SD]) and median (range). χ² and Fisher’s exact tests were conducted to determine differences in CINV events and HCRU between HEC and MEC regimens. This is a retrospective study; the comparisons presented are for trends and/or informative purposes only. All ‘significance’ results should be qualified as such. There is no scientific basis for statistical significance claims between retrospective groups.

In total, 1587 patient records met the inclusion criteria, 1299 of whom received HEC (AC, n = 1247; cisplatin, n = 52), and 288 of whom received MEC (carboplatin) (Figure 1). The analysis population was mainly women (91%), the mean age of patients at the time of their first line of chemotherapy was 54.8 years, and most patients (79%) had breast cancer (Table 2). The mean comorbidity index was 1.0 for all patients at diagnosis, and 1.9 at the start of the first line of chemotherapy. Most patients had commercial medical insurance plans (53%).

The most common first line of chemotherapy in the overall analysis population was an AC-containing regimen (79%), and the mean duration of first-line chemotherapy (time from start of first-line therapy until start of second-line therapy) was 10.8 months, although the duration of first-line chemotherapy was longer in the HEC group (12.3 months) than in the MEC group (4.1 months). The mean time to discontinuation of first-line chemotherapy over cycles 1–4 was 6.9 months. The mean number of treatment cycles overall was 3.5, with a median of 4 (range 1–16). For the HEC and MEC groups, the median (range) numbers of chemotherapy cycles administered were 4 (1–10) and 3 (1–16), respectively. Chemotherapy regimens, durations of therapy and mean number of cycles by HEC and MEC subgroups are shown in Table 3.

Table 4 shows antiemetic regimens administered during the first line of chemotherapy, overall and by HEC and MEC subgroups. In the HEC group, the most common prophylactic antiemetic regimen (in 92% of patients) was an iv. NK-1 RA plus palonosetron plus dexamethasone; in the MEC group, the most common antiemetic regimen (in 52% of patients) was palonosetron plus dexamethasone.

The frequency of CINV events across all cycles by patient and by patient cycle for HEC and MEC groups is shown in Figure 2. There was a significant difference between HEC and MEC groups for CINV events by patient cycle, with CINV events in 40% of HEC cycles and 44% of MEC cycles (p = 0.01). At the patient level, there was no significant difference in the proportion of patients experiencing CINV events between the HEC (51%) and MEC (52%) groups.

In cycle 1 only, a significantly lower proportion of patients had CINV events in the HEC group than in the MEC group at the patient level (39 vs 45%; p = 0.04).

Across all cycles at the patient cycle level, there was no difference in the frequency of clinic visits for any reason between HEC (97%) and MEC (96%) groups. Across all cycles at the patient level, the majority of patients had clinic visits for any reason, but the proportion was higher among patients receiving HEC than among patients receiving MEC (99 vs 97%, respectively; p = 0.01). Clinic visits due to CINV were not significantly different at the patient cycle level between HEC (38%) and MEC (40%) groups, but significantly more patients receiving HEC than MEC (48 vs 42%, respectively; p = 0.05) had a CINV-related clinic visit (Figure 3).

The proportions of patients with ER visits for any cause and for CINV were low overall. However, across all cycles, significantly more patient cycles in the HEC group had an ER visit for any cause compared with the MEC group (8 vs 5%; p = 0.05), although there was no significant difference between HEC (13%) and MEC (14%) groups in any-cause ER visits at the patient level. For ER visits due to CINV, there was no significant difference between HEC and MEC groups at the patient cycle level or at the patient level (Figure 4).

The proportions of hospitalizations for any reason and for CINV were low overall. There were no differences at the patient cycle or patient level between HEC and MEC groups in the frequency of hospitalizations for any cause or due to CINV across all cycles (Figure 5).

For cycle 1 only, clinic visits for any reason (scheduled or unscheduled) were significantly higher in the HEC group than in the MEC group (98 vs 95%; p = 0.01), but there was no difference in the proportion of patients with CINV-related clinic visits between the HEC and MEC groups (37 vs 40%, respectively).

The frequency of ER visits in cycle 1 was low overall. There was no difference between HEC and MEC groups in the percentage of patients with at least 1 ER visit for any reason (7 vs 8%, respectively) and for CINV (3 vs 4%, respectively).

The incidence of hospitalization during cycle 1 was low. A lower proportion of patients in the HEC group than in the MEC group had hospitalizations for any reason (2 vs 5%; p < 0.01) and because of CINV (1 vs 3%, respectively; p < 0.01).

Antiemetic regimen changes were recorded as either unscheduled changes, in other words, a new ‘rescue’ medication administered in the clinic from day 2 after chemotherapy administration and in addition to the prescribed antiemetic regimen, or a scheduled (deliberate) change to the prescribed prophylactic antiemetic regimen.

Across all cycles, significantly more patient cycles in the HEC group than in the MEC group had unscheduled iv. antiemetic regimen changes (41 vs 35%, respectively; p < 0.05). A similar result was also found at the patient level for all cycles (39 vs 27%, respectively; p < 0.05) (Figure 6A). Moreover, in cycle 1 only, a significantly higher proportion of patients in the HEC group than in the MEC group had unscheduled iv. antiemetic regimen changes (39 vs 27%, respectively; p < 0.01).

Regarding deliberate changes to the prophylactic antiemetic regimens prescribed, there were significantly more changes for the HEC versus MEC groups over all the cycles at the patient cycle level (13 vs 9%, respectively; p < 0.05) and at the patient level (33 vs 22%, respectively; p < 0.05) (Figure 6B).

Across all cycles, antiemetic efficacy was significantly higher in the HEC group than in the MEC group at the patient cycle level (40 vs 35%; p = 0.01) and at the patient level (38 vs 27%, respectively; p < 0.05). Findings for cycle 1 only were similar; antiemetic efficacy was significantly higher in the HEC group compared with the MEC group (38% of patients vs 27%, respectively; p < 0.01).