Adherence to prescribing restrictions for HER2-positive metastatic breast cancer in Australia: a national population-based observational study (2001-2016)

Abstract

Background Targeted cancer therapy is often complex, involving multiple agents and chemotherapeutic partners. In Australia, prescribing restrictions are put in place to reflect existing evidence of cost-effectiveness of these medicines. As therapeutic options continue to expand, these restrictions may not be perceived to align with best practice and it is not known if their use in the real-world clinic adheres to these restrictions. We examined the treatment of women receiving trastuzumab for HER2-positive metastatic breast cancer (HER2+MBC) to determine the extent to which treatment adhered to national prescribing restrictions. Methods and findings Our population-based, retrospective cohort study used dispensing records for every Australian woman initiating trastuzumab for HER2+MBC between 2001-2013, followed through 2016. We used group-based trajectory models (GBTMs) to cluster patients, first on their patterns of trastuzumab exposure, and then on their patterns of lapatinib and chemotherapy exposure. We described the characteristics of patients within each cluster, and examined their treatments and combinations of treatments to determine restriction adherence. Of 5,052 patients initiating trastuzumab, 1,795 (36%) received at least one non-adherent HER2-targeted treatment. The most common non-adherent treatments were trastuzumab combinations involving vinorelbine (24% of non-adherent treatments); capecitabine (24%); and anthracyclines (10%). Non-adherent lapatinib use was observed in 4% of patients. GBTM identified three trastuzumab exposure clusters, each containing three further sub-clusters. The largest proportions of non-adherent treatments were in sub-clusters with longer trastuzumab exposure and more non-taxane chemotherapy. Patients in these sub-clusters were younger than those in sub-clusters with less non-adherent treatment. Conclusions Our study highlights that, even during the relatively simpler treatment era of our study period, a substantial amount of treatment did not adhere to prescribing restrictions. As more trials are conducted exploring pertuzumab and T-DM1 in combination with different chemotherapies and other HER2-targeted therapies, the regulation and funding of HER2-targeted treatment will become more challenging.

Trastuzumab emtansine for HER2-positive metastatic breast cancer: Outcomes from a whole-of-population Australian cohort

“…The high proportion of patients treated with first-line T-DM1 who received (neo)adjuvant trastuzumab in our cohort (81%) likely reflects Australian prescribing restrictions for T-DM1 that require patients to relapse on or within 6 months of completing adjuvant trastuzumab in order to access first-line T-DM1, and overall, T-DM1 appears to have been used largely within Australian prescribing restrictions [ 22 ]. This finding is an interesting contrast to our previous research examining adherence to the prescribing restrictions around trastuzumab during the Herceptin Program, where we found a large proportion of treatment outside the prescribing restrictions [ 23 ].…”

The changing face of Australian data reforms: Impact on pharmacoepidemiology research

“…In July 2019, quality use of medicines and medicines safety was announced as Australia's tenth national health priority [28,29]. Studies catalogued in this systematic review provide contemporary evidence assessing quality use of medicines including the impact of medicines policy interventions, [30][31][32] medicine use in populations not always represented in clinical trials, [33,34] and adherence with current treatment guidelines [35][36][37]. However, there is a need for greater focus on outcomes studies, especially pertaining to medicine safety, and with greater attention to vulnerable population sub-groups [38].…”