March 2018 VOL 9, NO 3

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San Antonio Breast Cancer Syposium

CDK4/6 Inhibitors Effective in Older Women, But with More Side Effects

Older patients with hormone receptor–positive, HER2-negative, metastatic breast cancer derive similar benefit as younger patients treated with CDK4/6 inhibitors as part of initial endocrine therapy, according to a pooled analysis of registration trials presented at the 2017 San Antonio Breast Cancer Symposium.

Across pooled trials, the rates of selected adverse events were similar, but women aged ≥65 years, as well as those aged ≥75 years, had higher rates of more severe adverse events as well as dose modifications and interruptions.

“Accrual of older women to clinical trials is challenging. Women over age 75 make up about 4% of the clinical trial population and are underrepresented. Over 40% of breast cancer–related deaths are in women age 70 and older. We have limited data on the safety and efficacy of CDK4/6 inhibitors in older adults,” said lead author Harpreet Singh, MD, Office of Hematology and Oncology Products at the FDA.

The retrospective study included registration trials submitted for CDK4/6 inhibitors in combination with an aromatase inhibitor (AI) as initial endocrine-based therapy for advanced or metastatic breast cancer. The pooled efficacy population was 1992 patients, and progression-free survival (PFS) was evaluated in 329 patients aged ≥70 years in the treatment and control groups.

For patients aged ≥70 years treated with a CDK4/6 inhibitor plus AI, median PFS was not reached. For patients aged <70 years, median PFS was 23.75 months.

“There seems to be a similar benefit no matter what the age of patients,” Dr Singh stated. “No treatment differences were observed across age subgroups.”

Safety and tolerability were assessed in all patients who received at least 1 dose of a CDK4/6 inhibitor. Twenty-five percent were aged ≥70 years (5% of these were aged ≥80 years).

Higher rates of adverse events occurring up to 30 days from the last dose were observed in patients aged ≥65 years and in patients aged ≥70 years. Grade 3/4 adverse events were reported in 66% of patients aged <65 years compared with 80% for those aged ≥65 years and 85% for those aged ≥70 years. Adverse events leading to treatment discontinuation were reported in 8%, 16%, and 17%, respectively. Serious adverse events were reported in 16%, 31%, and 33%, respectively.

Looking at selected adverse events, the rates of neutropenia and hepatotoxicity were similar across age-groups, whereas rates of infection, fatigue, and diarrhea trended slightly higher in the older patients.

“The eligibility criteria for clinical trials need to be revised and should be based partly on patient-reported outcomes and real-world data,” she said.

“Age is one factor we consider when selecting patients for CDK4/6 inhibitor therapy. The patients we tend to treat with these agents in addition to endocrine therapy are those with higher disease burden who are more fit and younger. These data provide some reassurance about the efficacy of CDK4/6 inhibitors in the older population and reinforce our concerns, namely more side effects. The patients in this analysis are not reflective of those we see in clinical practice. We need to assess safety in older patients who are less fit,” said Joseph Sparano, MD, Montefiore Medical Center, New York City.

“A single endocrine agent might be sufficient for an 85-year old with a few comorbidities,” said Rowan Chlebowski, MD, City of Hope, Duarte, CA.

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