Background and Importance Abemaciclib in combination with endocrine therapy (ET) has recently been authorised for adjuvant treatment of patients with human epidermal growth factor receptor 2 (HER2) negative and luminal early breast cancer (EBC) at high risk of recurrence.
Aim and Objectives To assess the comparative efficacy between abemaciclib and palbociclib in HER2-negative, high risk of recurrence and luminal EBC patients and to establish whether these drugs can be considered equivalent therapeutic alternatives (ETA), through an adjusted indirect treatment comparison (ITC).
Material and Methods A bibliographic search was conducted to identify phase III clinical trials with abemaciclib or palbociclib as adjuvant treatment in a similar EBC population (luminal type, HER2-negative and high risk of recurrence), duration and endpoints. The primary endpoint was invasive disease-free survival (IDFS) and ET was used as a common comparator. Similar clinical trials, consistent results and efficacy demonstration against the common comparator (ET) were required for the adjusted ITC.
Results Two trials were included, one of each drug. Both of them were phase III trials, randomised, in patients with HER2-negative, high risk and luminal EBC. Differences were found in the trial design (abemaciclib open-label vs palbociblib double-blind), number of patients included (abemaciclib N=5637 vs palbociclib N=1250), treatment duration (abemaciclib two years vs palbociclib one year) and percentage of patients pretreated with taxane, anthracycline or both (abemaciclib 37% vs palbociclib 99%). Clinical trials were not similar due to these differences.
Abemaciclib was effective in HER2-negative, high risk and luminal EBC. However, palbociclib was not. IDFS abemaciclib group was statistically significant (HR=0.70; 95% CI: 0.59-0.82; p<0.0001) with a median follow-up of 27 months (90% patients completed treatment). In contrast, IDFS palbociclib group was not statistically significant (HR=0.93; 95% CI: 0.74-1.17; p=0.525) with a median follow-up of 43 months (92% patients completed treatment).
Regarding consist results, 2-year IDFS rate was different too: abemaciclib 93% vs palpociclib 88%. In short, relevant methodological limitations were detected so adjusted ITC was not possible.
Conclusion and Relevance Abemaciclib and palbociclib cannot be considered ETA in HER2-negative, high risk and luminal EBC, although abemaciclib demonstrated efficacy as adjuvant treatment in these patients.
Conflict of Interest No conflict of interest.