Prospective cohort study of palbociclib in HR+/HER2- metastatic breast cancer in Japan.

Abstract

1056 Background: The combination of palbociclib (PAL) with an aromatase inhibitor or fulvestrant has been shown to improve progression-free survival (PFS) in hormone receptor (HR)-positive and human epidermal growth factor receptor (HER2)-negative metastatic breast cancer. However, the addition of PAL to endocrine therapy increases toxicity and cost compared to endocrine therapy alone. In addition, PAL treatment may affect the efficacy of subsequent treatments, as its benefit in terms of overall survival (OS) has not yet been demonstrated. Therefore, it is crucial to prospectively evaluate whether PAL can improve clinical outcomes and quality of life (QoL) for patients in a real-world setting. Methods: A prospective observational study of PAL is planned in three cohorts (A, B, and C) categorized by line of endocrine treatment (1st, 2nd, or 3rd or later line) for postmenopausal metastatic or unresectable breast cancer. The primary endpoint is PFS in each line of treatment. For cohort B, PFS2 is defined as time from initiation of first-line therapy for metastatic disease. Based on the results of the PALOMA-2 and -3 studies, the planned sample size was set at 700 cases with confidence intervals: 340 in cohort A, 200 in cohort B and 130 in cohort C. Secondary endpoints include OS, clinical benefit rate, time to chemotherapy, adverse events (AEs), patient-reported outcomes and health-related quality of life, which will also be evaluated during follow-up. This study aims to determine whether the efficacy, safety and QoL outcomes of PAL treatment in daily clinical practice are comparable to those observed in clinical trials, and whether PAL affects the efficacy and safety of subsequent treatments. This report presents PFS results from each cohort. An exploratory analysis of OS rates from the start of 1st-line therapy for metastatic disease is also reported. Results: A total of 700 patients were enrolled from April 2019 to January 2023. After excluding cases with contraindications, the final cohort distribution was as follows: 246 in cohort A, 282 in cohort B, and 65 in cohort C. The median PFS was 25.8 months (95% CI: 21.4) for cohort A, 18.0 months (95% CI: 14.0-22.7) for cohort B, and 12.0 months (95% CI: 7.7-17.4) for cohort C. The median PFS2 for cohort B was 57.9 months (95% CI: 45.2-65.1). The 3-year OS rates for cohorts A and B from the start of 1st-line metastatic therapy were 76.3% and 93.1%, respectively. Conclusions: The PFS result for the 1st-line cohort (Cohort A) was nearly equivalent to the 24.8 months observed in PALOMA-2, while the 2nd-line cohort (Cohort B) showed markedly better results than the 9.5 months reported in PALOMA-3. Although the background of each cohort needs to be further investigated, the PFS2 result of Cohort B was excellent and the subsequent 3-year OS of this cohort was satisfactory. Based on these results, the use of PAL in the 2nd line setting may be clinically acceptable. Clinical trial information: UMIN000035863 .