Despite differences in tumors, the addition of CDK 4/6 inhibitors to endocrine therapy showed a benefit in patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer compared with endocrine therapy alone.
Adding CDK 4/6 inhibitors to endocrine therapy for patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer showed a survival benefit despite patients having differences in their tumors, according to a study published in Lancet Oncology.
“To our knowledge, this is the first comprehensive pooled analysis of all marketed CDKIs (CDK 4/6 inhibitors) to assess efficacy in these less common subgroups of patients with breast cancer,” researchers from the Food and Drug Administration (FDA) wrote. The researchers decided to investigate if there was a benefit because the addition of CDK inhibitors can be costly to patients.
Furthermore, the current American Society of Clinical Oncology endocrine therapy guidelines for treating patients with metastatic breast cancer call for CDK inhibitor-based therapy in the first- and second-line settings.
The study included pooled individual patient data from all phase 3 randomized breast cancer trials of CDK inhibitors plus endocrine therapy submitted to the FDA before Jan 1, 2019.
The researchers then investigated pre-specified subgroup analyses from the phase 3 trials in patients with progesterone receptor-negative disease, patients with a disease-free interval of 12 months or less, patients with de-novo metastases, patients with lobular histology and bone-only disease.
Although researchers hypothesized that patients with lobular breast cancer or bone-only metastatic disease would respond well to endocrine therapy alone, and therefore derive a lesser benefit from the addition of CDK inhibitors, they ultimately found that all subgroups of patients benefited from the addition of CDK inhibitors.
“Our results in fact showed that all subgroups of patients derived similar benefit from the addition of a CDKI to endocrine therapy in this setting and that positive hormone receptor status remains the best predictive biomarker for the benefit of addition of CDKIs to endocrine therapy,” the researchers explained. Across the pooled data, researchers found an estimated difference of 8.8 months in progression-free survival or the time a patient lived without disease worsening, in favor of CDK 4/6 inhibitors over placebo in addition to endocrine therapy, showing a similar treatment effect regardless of the subgroup.
“Although the findings of these studies are hypothesis-generating, further research is needed to confirm whether these or other candidate biomarkers are predictive of response across the class of CDK inhibitors and in the first-line and in the second-line and beyond settings,” the researchers explained.
They added that it’s important to follow these results as they mature and to continue assessing other biomarkers that could also indicate whether patients with metastatic breast cancer need CDK inhibitors along with their endocrine therapy.