A multicentre study with real-world data of the use of palbociclib in the treatment of breast cancer: Treatment duration correlates with dose reductions

Abstract

Objective Palbociclib, a highly selective reversible CDK4-6 kinase inhibitor, is indicated in combination with an aromatase inhibitor or in combination with fulvestrant in women who had received prior endocrine treatment. Studies have demonstrated the efficacy of palbociclib in combination with fulvestrant in increasing progression-free survival in patients who relapsed or progressed on previous endocrine therapy, or in combination with aromatase inhibitor in patients who had not received previous treatments. We analysed the prescribing patterns of palbociclib in real practice correlating it with the evidence of treatment-related toxicity management and to time-to-treatment discontinuation and treatment adherence. Methods For the observational, retrospective study, data were collected from five Italian hospital centres that prescribed palbociclib between April 2017 and April 2020. Each centre provided data derived from an administrative database of adult patients treated with palbociclib for the two therapeutic indications. Treatment adherence was calculated using the proportion of days covered method while time-to-treatment discontinuation was defined as the difference between the first and last date treatment was administered plus the days ideally covered by the last date treatment was given. Results There were 375 patients enrolled during the study period, of whom 159 were treated with palbociclib and aromatase inhibitor and 216 were treated with palbociclib and fulvestrant. The time-to-treatment discontinuation was 8.9 months in the case of P + f (95% CI: 7.1−12.7) and 13.7 months in the case of P + ia (95% CI: 8.9−17.5). In both cohorts, treatments that received at least one dose reduction had a statistically higher time-to-treatment discontinuation than those without dose reduction (17.7 months vs. 9.2 and 16.6 vs. 7.4). The mean adherence in our study was 0.9 and remained high in treatments with one dose reduction (0.83) and this with two dose reductions (0.87). Conclusion Based on these findings, it appears that the management of toxicities through reducing doses, as required by the Summary of Product Characteristics, results in a better outcome in terms of therapy duration, and therefore time to failure due to progression or toxicity.

Overall survival in Japanese patients with ER+/HER2− advanced breast cancer treated with first-line palbociclib plus letrozole

“…In our analysis, patients with palbociclib plus letrozole treatment duration ≥ 24 months had longer median OS than those with treatment duration < 24 months, further supporting the association of palbociclib plus letrozole use and OS benefit. A longer duration of exposure to the study treatment may have been achieved in part through dose management as palbociclib treatment duration has been shown to correlate with dose reductions [ 21 ]. The relationships between patient OS and palbociclib treatment patterns and duration warrant further investigation.…”