Abstract P3-07-09: Prevalence and effects of off-label use of chemotherapeutic agents in elderly breast cancer patients: estimates from Surveillance, Epidemiology and End Results-Medicare data

Abstract

Abstract Purpose: To gain FDA approval, drug companies submit evidence from clinical trials demonstrating that a drug is safe and efficacious in a certain setting. Current regulations allow oncologists to prescribe approved drugs for uses other than those for which the drug was approved (off-label use). While there seems to be a consensus that off-label use is common in oncology, there is a lack of published data on recent trends and on utilization in different populations. The strength of evidence demonstrating safety and efficacy varies for drugs used in the off-label setting, and patients may be at risk for unacceptable toxicity. The risk of toxicity may be higher among older patients, whose ability to tolerate chemotherapy is compromised by age-related organ decline and comorbidities. Our objective was to describe the prevalence of off-label use of chemotherapeutic agents in elderly breast cancer patients with Medicare coverage and to compare toxicity between patients using off-label drugs and patients using only approved drugs. Materials and Methods: We identified women 65 and older with a first primary breast cancer diagnosed in 2000–2007 from Surveillance, Epidemiology and End Results (SEER) cancer registry data linked with Medicare claims. Specific chemotherapeutic agents used following diagnosis were identified in Medicare claims and classified as on- or off-label use based on whether the drug was approved for breast cancer as of May 2012. Thirty-day toxicity (ER visit, hospitalization or death) was compared between patients whose first line regimen contained only approved drugs and patients whose first line regimen contained at least one off-label drug using the Cochran-Mantel-Haenszel test. Results: The most commonly-used approved drugs were cyclophosphamide (used in 14% of patients), doxorubicin (10%), docetaxel (5%), fluorouracil (5%), and paclitaxel (5%). In total, forty-five off-label agents were used. Vinorelbine and carboplatin were each used in 1% of patients. No other off-label drug was used in more than 109 (0.11%) of patients. Toxicity was significantly higher for patients treated with off-label agents compared to patients treated with only approved drugs, after adjusting for stage at diagnosis (p = 0.01). Conclusions: In this population-based cohort, rates of chemotherapy use were generally low, and rates of off-label use were even lower, with only 3% of patients treated off-label. Off-label use became more common as stage at diagnosis increased, with use increasing from 1% in stage 0/1 patients to 12% in stage 4 patients. The higher toxicity rates observed in patients treated with off-label drugs may indicate that these drugs are less safe than approved agents. This result will be confirmed in a matched analysis accounting for age, stage and comorbidities. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-07-09.