A comparison of the adherence and persistence of patients with metastatic colorectal cancer to oral combination therapy with trifluridine and tipiracil (FTD + TPI) and oral regorafenib (REG) showed that patients were more likely to be adherent to and persist in taking FTD + TPI. The findings from this study were published in The Oncologist.

Current management of patients with disseminated metastatic colorectal cancer involves treatment with various drugs or treatment regimens administered over multiple lines of therapy, and represents a continuum of care. Options in the therapeutic armamentarium for metastatic colorectal cancer include oral agents, such as the combination of FTD + TPI, which interferes with DNA synthesis, and REG, a multi-tyrosine kinase inhibitor.

Because both of these therapies have identical FDA indications for the treatment of metastatic colorectal cancer, regorafenib is sometimes administered prior to FTD + TPI and vice versa.

The aim of this study was to evaluate the adherence and persistence of patients with metastatic colorectal cancer with respect to these 2 oral therapies, and to assess whether their sequence of administration affects these parameters, as well as time to discontinuation.

Medication adherence was based on prescription refill information using the medication possession ratio (MPR) — the ratio of number of days of index medication provided to the number of days between the first day of the first prescription and the last day supply of the last prescription — and the proportion of days covered (PDC) — the number of unique days of index medication divided by a fixed time interval in days. A patient with an MPR or PDC of 0.80 or greater was considered adherent to the index treatment. Medication persistence was based on continuous use of the index medication within a fixed period of time, and time to discontinuation was evaluated over the entire observation period, both using allowable gap thresholds of 45 and 60 days.

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This retrospective longitudinal cohort study included 469 and 311 adult patients with metastatic colorectal cancer included in a large non-payer-owned insurance claims database who initiated therapy with FTD + TPI and REG, respectively, after October 2015.

A key finding of this study was that mean MPR was significantly higher for users of FTD + TPI compared with REG (0.83 vs 0.86; P <.001). In addition, the mean PDCs at 3 months (0.72 vs 0.60; P <.001) and 6 months (0.56 vs 0.48; P =.020) were also significantly higher for users of FTD + TPI vs REG.  Furthermore, significantly higher medication persistence rates were also observed for FTD + TPI compared with REG users (P <.001), and after adjustment for baseline factors, the risk of medication discontinuation was significantly lower for users of FTD + TPI vs users of REG when a gap of 45 days (P =.006), but not 60 days, was allowed.

Regarding medication sequencing, 96 patients in the study cohort switched from FTD + TPI to REG and 83 patients switched from REG to FTD + TPI. When these 2 subgroups were compared, mean MPR (0.88 vs 0.79; P =.003), mean PDC at 3 months (0.87 vs 0.75; P <.001), mean PDC at 6 months (0.73 vs 0.62; P <.001), persistence to the first medication at 3 months (93.7% vs 71.1%; P <.001; 45-day gap), and time to treatment discontinuation (107 vs 81 days; P <.001; 45-day gap) were all significantly higher in the former subgroup. However, persistence to the first medication at 6 months was not significantly different when the 2 subgroups were compared.

In their concluding remarks, the study authors commented that “these findings can help inform treatment decisions with respect to the choice and sequencing of treatment with FTD + TPI and REG in patients with metastatic colorectal cancer.”

Reference

Patel AK, Barghout V, Yenikomshian MA, et al. Real-world adherence in patients with metastatic colorectal cancer treated with trifluridine plus tipiracil or regorafenib [published online October 7, 2019]. Oncologist. doi: 10.1634/theoncologist.2019-0240