CDK4/6 inhibition in high-risk early breast cancer

CDK4/6 inhibitors (plus endocrine therapy) have shown to improve overall survival of patients with ER-positive/HER2-negative breast cancer who progressed on endocrine therapy [1-3]. First results of the monarchE trial showed abemaciclib to improve disease-free survival in patients with early, high-risk, ER-positive/HER2-negative breast cancer [4]. In contrast, in the PALLAS trial, palbociclib did not [5].

In the open-label, phase 3 monarchE trial, 5,637 patients with early, high-risk ER-positive/HER2-negative breast cancer were 1:1 randomised to abemaciclib (150 mg twice daily for 2 years) plus endocrine therapy or endocrine therapy alone. Abemaciclib plus endocrine therapy demonstrated a significant improvement in invasive disease-free survival (iDFS) versus endocrine therapy alone (HR 0.747; P=0.0096), corresponding to a 25.3% reduction in the risk of an IDFS event (see Figure). The 2-year iDFS rates were 92.2% versus 88.7%, respectively. Consistent benefit was seen in all prespecified subgroups.

Likewise, in the phase 3 PALLAS trial, 5,760 patients were randomised to receive either 2 years of palbociclib with adjuvant endocrine therapy or endocrine therapy alone. After a median follow-up of 23.7 months (351 events), iDFS was similar between the two arms, with 3-year iDFS of 88.2% for palbociclib plus endocrine therapy, and 88.5% for endocrine therapy alone (HR 0.93).

Figure: Invasive disease-free survival results of monarchE [4]

1. Turner NC, et al. N Engl J Med 2018;379:1926-1936.
2. Sledge GW, et al. JAMA Oncol. 2019;6:116-124.
3. Slamon DJ. et al. N Engl J Med 2020;382:514-524.
4. Johnston SRD, et al. Abemaciclib in high risk early breast cancer. ESMO 2020 Virtual Meeting, abstract LBA5.
5. Mayer EL, et al. PALLAS: A randomized phase III trial of adjuvant palbociclib with endocrine therapy versus endocrine therapy alone for HR+/HER2- early breast cancer. ESMO 2020 Virtual Meeting, abstract LBA12.

Posted on 25 November 202016 February 2024