New-Generation Breast Cancer Drugs, CDK 4/6 Inhibitors, Are Effective in Both Younger and Older Patients

For women with hormone receptor-positive, HER2-negative metastatic breast cancer, as first-line treatment, a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor and aromatase inhibitor combination was evaluated for efficacy and safety in a presented study. Journal of Clinical Oncology published the findings, including data from 3 randomized clinical trials. Older and younger postmenopausal women benefited similarly, but older women experienced more side effects.

Combining standard hormonal breast cancer treatment with a CDK 4/6 inhibitor is currently considered standard first-line treatment for postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, a breast endocrine therapy regimen consisting of a CDK 4 / 6 inhibitor (such as palbociclib, ribociclib, abemaciclib) given concurrently with an aromatase inhibitor or fulvestrant .

Despite the high proportion of older women with breast cancer, this group—particularly those aged 75 and older—has been underrepresented in clinical trials . Clinical data addressing older patients being considered for endocrine treatment combined with a CDK4/6 inhibitor are therefore limited.

This analysis included 3 clinical trials and a total of 1105 patients:

• PALOMA-2: letrozole with or without palbociclib (Ibrance),
• MONALEESA-2: letrozole with or without ribociclib (Valamor), and 
• MONARCH-3: anastrozole or letrozole with or without abemaciclib (Verzenios).

In this population, 456 (25%) and 198 (10.8%) patients were at least 70 or 75 years old, respectively. All 3 trials had progression-free survival as their primary endpoint. All patients were postmenopausal, had not previously been treated for metastatic disease and had a general performance status of ECOG 0 or 1 .

Analysis Results

• For all patients in the analysis, median progression-free survival with an aromatase inhibitor alone was 14.8 months , and for those treated with an aromatase inhibitor combined with a CDK 4/6 inhibitor it was 27.7 months.
• The corresponding results for patients aged 70 and older were 19.2 months and 33.1 months, and for those over 75, 13.7 months and 24.9 months.
• Patients over 75 and those under 75 were compared for side effects , with higher serious (grade 3 and 4) side effects in older patients: 88.8% versus 73.4%.
• In addition, patients aged 75 and older more frequently experienced dose reduction / omission (81.6% – 71.1%) and treatment discontinuation (32.0% – 12.1%).
• Patients aged 75 and older treated with an aromatase inhibitor combined with a CDK 4/6 inhibitor experienced more diarrhea (53.6% versus 45.5%) and fatigue (54.4% – 44.3%). 
• For patients aged 70 and older receiving combination treatment, dose reduction / interruption was more common during cycles 1 to 3, and neutropenia, diarrhea and increased creatinine were the most common side effects associated with dose reduction / interruption.

In conclusion, breast cancer patients in older age groups receive similar benefits from CDK 4/6 inhibitors. Supportive care measures and closer side effect management may improve tolerability of this regimen in older patients.

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