Prevalence and Safety of Off-Label Use of Chemotherapeutic Agents in Older Patients With Breast Cancer: Estimates From SEER-Medicare Data

Abstract

Background: Prescribing drugs outside of the label indication is legal and may reflect standard practice; however, some off-label use may be inappropriate. This study measured the prevalence and safety of off-label use both in accordance with practice guidelines and inconsistent with practice guidelines in older patients with breast cancer.

Patients and methods: The SEER-Medicare data set was used to identify women diagnosed with breast cancer. Intravenous chemotherapy was identified using Medicare claims and classified as either on-label, off-label but included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer ("off-label/supported"), or off-label and not included in the NCCN Guidelines ("off-label/unsupported"). Hospitalization/emergency department (ED) admission rates were compared.

Results: A total of 13,347 women were treated with 16,127 regimens (12% of women switched regimen); 64% of regimens were off-label/supported, 25% were on-label, and 11% were off-label/unsupported, and hospitalization/ED admission occurred in 27%, 25%, and 32% of regimens, respectively (P<.0001). Drugs never included in the NCCN Guidelines for Breast Cancer accounted for 19% of off-label/unsupported use (1% of total use).

Conclusions: Off-label use without scientific support was not common, whereas 64% of use was off-label/supported, reflecting the fact that widely accepted indications are often not tested in registration trials. Off-label/supported use will likely increase as more drugs are expected to have activity across cancer sites, and therefore understanding the implications of such use is critical.

Figure 1

FDA Approval and NCCN Guideline Information by year for intravenous chemotherapies. Figure 1A shows approval timelines for the adjuvant treatment of early stage breast cancer (Stage I-III) and Figure 1B shows approval timelines for advanced stage breast cancer (stage IV metastatic). Dark blue indicates years during which the agent was FDA approved and NCCN supported, light blue indicates years during which the agent was FDA approved but not NCCN supported, and white indicates years during which the agent was NCCN supported but not FDA approved. Blank spaces indicate years during which the agent was neither approved nor supported. An asterisk next to an agent name indicates that the agent was never FDA approved for that stage of disease at any time during the study period.

Figure 2

The two sample scenarios below demonstrate the algorithm used to separate dated chemotherapy claims into regimen lines. A, B, and C represent different agents.

Figure 3

Percent of regimen lines off-label/unsupported versus total number of regimen lines, by agent. Only agents that were used in at least 24 regimen lines are included. Most agents were either used in very few regimen lines but with almost 100% of uses being off-label or used in many regimen lines with almost 100% of uses being on-label. For agents with 40-60% of uses off-label, the total number of regimen lines in which they were used is shown next to the agent name.

Figure 4

Hospitalization and ER admission rates by indication category and stage, matched analysis