Background

Breast cancer is the most common cancer in women worldwide, with more than two million new cases diagnosed in 2018. The UK has the eighth highest rate per 100,000 population, with 93.6 cases per 100,000 (World Cancer Research Fund 2021).

Overall survival rates for breast cancer vary worldwide, but in general they have improved, and in the UK they have doubled over the past 40 years (Cancer Research UK 2021). In England, around 85% of women diagnosed with breast cancer survive for five years or more, and when diagnosed at its earliest stage, 98% of women survive for five years or more. However, this survival rate falls to 26% when breast cancer is diagnosed at its latest stage (Cancer Research UK 2021), known as stage IV or metastatic breast cancer.

The low survival rate for metastatic breast cancer is in part because management of the condition remains challenging due to the varying responses of the condition to treatment. However, there have been some positive developments for patients with metastatic breast cancer in the form of a new class of anticancer drugs known as cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors, which are given in conjunction with hormone therapy. These are oral medicines that disrupt cancer cell proliferation and offer certain advantages to patients with metastatic breast cancer, for example delaying the use of chemotherapy in some women for up to two years (Rugo et al 2019). The first two CDK 4/6 inhibitors were approved for use in the UK by the National Institute for Health and Care Excellence (NICE) in 2017, with a third following in 2019 (NICE 2017a, 2017b, 2019).

Aim

To document local practice with regard to the use of the three available CDK 4/6 inhibitors for patients with metastatic breast cancer.

Method

The trust’s electronic prescribing system was used to search for patients with metastatic breast cancer who were receiving anticancer therapy in the form of one of the three CDK 4/6 inhibitors. An electronic search was conducted in February 2020 by the cancer centre’s information officer. The search included all patients who had been on these drugs from the time they were first approved in 2017, until the end of December 2019. There were no exclusion or inclusion criteria.

Once patients were identified, a retrospective examination of their case notes was undertaken to obtain information related to their use and experiences with CDK 4/6 inhibitors. All patient details were anonymised at source. The audit intended to document practice with regard to the use of CDK4/6 inhibitors, including:

Results

The search identified 41 patients with metastatic breast cancer who were receiving anticancer therapy in the form of one of the three CDK 4/6 inhibitors. However, two were excluded due to lack of follow-up information and therefore 39 patients were included in the audit. The ages of the patients ranged from 33 years to 79 years, and all were female. Most patients had developed metastatic breast cancer as a result of a relapse from early breast cancer (n=27; 69%), while the remainder had metastatic breast cancer at first presentation (n=12; 31%)

Of the 27 patients who had relapsed from early breast cancer, 23 (85%) had received adjuvant chemotherapy, three patients had not, and one patient’s adjuvant chemotherapy status was unknown. The mean time to relapse was 11.4 years. Most of these patients had received fluorouracil, epirubicin hydrochloride, cyclophosphamide and docetaxel as their adjuvant chemotherapy regimen, which is in keeping with current practice (NICE 2018). The remaining patients received anti-hormonal therapy alone.

Of the three available CDK 4/6 inhibitor drugs, palbociclib was the most commonly prescribed (n=36). The two patients on ribociclib were excluded due to a lack of follow-up data. Figure 1 shows a breakdown of the patients’ medicines regimens.

Duration of treatment and dose reductions

Patients remained on CDK 4/6 inhibitor drugs for between one and 26 months. Six patients stopped therapy after one, five, ten (two patients), 11 and 13 months. Of these six patients, five stopped due to disease progression, and one stopped due to myelosuppression.

More than half the patients remained on their starting dose throughout their therapy, with 15 requiring a dose reduction due to mild side effects such as fatigue. Figure 2 demonstrates the 15 patients who required dose reductions, and how many cycles of treatment each patient completed before requiring a dose reduction.

Figure 2.

Completed cycles of treatment before dose reduction (n=15)

Figure 1.

Breakdown of the patients’ medicines regimens (n=39)

Six of the 15 patients who required a dose reduction did so after just two cycles of treatment. This was due to a reduction in their white cell counts, which was diagnosed following the regular blood tests that are required for all patients taking CDK 4/6 inhibitors. The remaining nine patients who required a dose reduction did so due to fatigue and/or anaemia.

Discussion

The introduction of CDK 4/6 inhibitors for the treatment of patients with metastatic breast cancer has enabled many to delay chemotherapy treatment. In addition, as an oral therapy, CDK 4/6 inhibitors offer advantages to patients when compared to intravenous (IV) therapy. For example, their mode of delivery means patients may not need admission to a ward for administration of the medicine. They also enable patients to self-administer the medicine at home, which has been reported to be preferred by patients (Oakley et al 2010).

In addition, oral medicines also offer advantages to the NHS. For example, by reducing the need to admit patients, the burden on inpatient beds and chemotherapy units is eased. There are also cost savings associated with oral medicines when compared with IV medicines (Oakley et al 2010).

However, it is important patients are educated about the drug they are being prescribed, and are provided with information on expected side effects, and when and how to take the medicine correctly (Oakley et al 2010). This is due to reports of patient safety issues relating to oral anticancer medicines resulting from errors such as incorrect doses being taken by patients who are self-administering at home (Oakley et al 2010). One potential solution is a home care model, whereby patients taking oral anticancer medicines are visited at home to assess and support them in taking their therapy. The trust is developing such a model that will incorporate assessment, support and medicine supply services in the community setting. Molassiotis et al (2009) found a home care programme to be more effective than standard care (standard care included simple education and written information on the drug) with regard to side effects.

This audit demonstrated the importance of early blood monitoring after starting patients on a CDK 4/6 inhibitor, with six patients requiring early dose reductions due to abnormalities detected on their blood results. However, beyond these six patients, there were few side effects reported. This finding is in line with the research into each of the three drugs, which found optimal side effect profiles for each drug relative to the control treatment in each study (Hortobagyi et al 2016, Rugo et al 2019, Johnston et al 2020).

The fact that palbociclib was the most commonly used CDK 4/6 inhibitor in the trust was likely due to the earlier licensing of the drug relative to the other two CDK 4/6 inhibitors. However, it should be noted that ribociclib requires additional monitoring with electrocardiograms, and that abemociclib is prescribed alongside fulvestrant (a drug that blocks oestrogen receptors), which is given via intramuscular injection. These extra considerations involved with the other two CDK 4/6 inhibitors may also have contributed to palbociclib being the preferred choice for the trust’s prescribing oncologist.

The length of treatment associated with CDK 4/6 inhibitors – some patients in the audit were receiving the drugs for up to 26 months – is likely to present some workload challenges for treatment clinics and clinical nurse specialists. For example, these patients require continued monitoring and support throughout their treatment; in addition, a shortage of clinical nurse specialists was identified in a survey by Breast Cancer Now (2017), which found that only 21% of organisations had one or more clinical nurse specialist dedicated to secondary breast cancer. To address this, patients receiving CDK 4/6 inhibitors are mostly assessed and supported by advanced nurse practitioners at the author’s trust.

Conclusion

CDK 4/6 inhibitors are a welcome addition to the treatment of metastatic breast cancer, and can delay the need for patients to receive chemotherapy. An audit of practice at a trust in England found that the drugs were well tolerated, with only six patients having to stop treatment altogether. Oral medicines such as these provide advantages to patients when compared to IV medicines, such as enabling them to self-administer the drug and reducing the need for admission to an inpatient bed.