No PEARLs of survival with palbociclib plus endocrine therapy compared with capecitabine, but QoL better

Although no overall survival (OS) benefit was observed in the final results of cohort 2 of the phase 3 PEARL study, combination therapy with CDK4/6 inhibitors plus endocrine therapy improved health-related quality of life (HR-QoL) and tolerability over chemotherapy for HR-positive, HER2-negative metastatic breast cancer progressing on aromatase inhibitors. The OS and HR-QoL results were presented for the first time at ESMO 2021 Congress.

The final results of the phase 3 PEARL study (NCT02028507), presented by Prof. Miguel Martín Jiménez (Complutense University of Madrid, Spain), compared palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with metastatic breast cancer who progressed on an aromatase inhibitor [1].

With a median follow-up of 28.0 months, the arm treated with palbociclib plus fulvestrant (n=149) had a median OS of 31.1 months, compared with 32.8 months in the arm treated with capecitabine (n=156) (HR 1.10; 95% CI 0.81–1.50; P=0.55; see Table). The results support earlier findings from the trial showing no progression-free survival (PFS) advantage for palbociclib plus fulvestrant over chemotherapy (HR 1.13; 95% CI 0.85–1.50) but an improved toxicity profile and a reduction in the time to deterioration of global health status [2].

Table: OS at median follow-up of 28.0 months shows no significant difference for palbociclib + fulvestrant versus capecitabine [1]



Despite the seemingly disappointing efficacy outcomes, the findings on HR-QoL based on patient-reported outcomes were significant. Differences were observed in the mean change in global health status (GHS)/QoL scores from baseline to treatment cycle 3 (2.9 for palbociclib/endocrine therapy vs -2.1 for capecitabine; P=0.007). Furthermore, the median time to deterioration in GHS/QoL was 8.3 months for palbociclib/endocrine therapy versus 5.3 months for capecitabine (HR 0.70; 95% CI 0.55–0.89; P=0.003). Similar improvements for palbociclib/endocrine therapy were also seen for other scales as physical, cognitive, social functioning, fatigue, nausea/vomiting, and appetite loss.

The most frequent grade 3–4 toxicities with palbociclib plus fulvestrant and capecitabine, respectively, were neutropenia (55.7% and 5.5%), hand/foot syndrome (0% and 23.5%), and diarrhoea (1.3% and 7.6%).

Prof. Martín Jiménez concluded that although there was no statistical superiority of palbociclib plus endocrine therapy over capecitabine with respect to PFS or OS in metastatic breast cancer patients resistant to aromatase inhibitors, palbociclib plus endocrine therapy showed a better safety profile and improved quality of life. The HR-QoL data were published 2 weeks following ESMO 2021 [3].

1. Martín Jiménez M, et al. Overall survival (OS) of palbociclib (P) plus endocrine therapy (ET) versus capecitabine (CAP) in hormone-receptor+/HER2- metastatic breast cancer (MBC) that progressed on aromatase inhibitors (AIs): Final results of the PEARL study. Abstract 229MO, ESMO Congress 2021, 16–21 September.
2. Martin M, Ann Oncol. 2021;32(4):488-499.
3. Kahan Z, et al. Eur J Cancer. 2021;156:70-82.

 

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Posted on 19 November 202127 March 2024