Although adjuvant therapy with CDK4/6 inhibitors has shown to benefit patients with advanced/metastatic HR-positive/HER2-negative breast cancer, the final analysis of the PALLAS trial shows no benefit of adjuvant palbociclib for patients with early HR-positive breast cancer.

Advances in the multidisciplinary care of HR-positive early breast cancer have markedly improved clinical outcomes. However, disease recurrence may still occur, particularly in patients with moderate- or high-risk cancers at the time of diagnosis. The use of CDK4/6 inhibitors combined with endocrine therapy is a standard of care for advanced breast cancer, supporting the rationale to study CDK4/6 inhibitors in the early breast cancer setting. PALLAS (NCT02513394) is a randomized, open-label, phase 3 trial in which patients with stage II-III HR-positive/HER2-negative early breast cancer received either 2 years of the CDK4/6 inhibitor palbociclib with adjuvant endocrine therapy or endocrine therapy alone. The primary endpoint was invasive disease-free survival (iDFS); secondary endpoints included distant recurrence-free survival (DRFS), locoregional recurrence-free survival (LRRFS), overall survival (OS), and safety. A total of 5,761 patients (median age 52 years, range 22-90) were enrolled; 1,014 (17.6%) had stage IIA disease and 4,728 (82.1%) stages IIB/III. Of all randomized patients, 4,754 (82.5%) had received prior (neo)adjuvant chemotherapy. After a protocol-planned second interim analysis in May 2020 crossed the futility threshold [1], Dr. Michael Gnant (Medical University of Vienna, Austria) now presented the results of the final analysis of PALLAS after a median follow-up of 31 months and 516 events recorded [2]. At the time of final analysis cut-off date (20 November 2020), iDFS was similar between the 2 treatment arms, with 3-year iDFS of 89.3% for palbociclib plus endocrine therapy and 89.4% for endocrine therapy alone (HR 0.96). There was no statistically significant difference in secondary outcome endpoints. Subgroup analyses revealed no significant interactions between treatment effect and other factors (including risk category). The safety profile of palbociclib was as expected, with grade 3 or 4 neutropenia the most common side effect. Overall, 42% of patients discontinued palbociclib prior to the planned 2-year duration, without an observed impact on survival outcomes. “With the full number of events, this analysis of the PALLAS trial shows that the addition of 2 years of palbociclib to ongoing adjuvant endocrine therapy does not improve survival endpoints for patients with stage II-III HR-positive/HER2-negative early breast cancer,” concluded Dr. Gnant. “Whether palbociclib is beneficial in the adjuvant setting for certain sub-groups of patients will be further evaluated with longer-term follow-up and by the ongoing translational science program.”

  1. Mayer EL, et al. Lancet Oncol. 2021;22:212-222.
  2. Gnant M, et al. Adjuvant palbociclib in HR+/HER2- early breast cancer: Final results from 5,760 patients in the randomized phase III PALLAS trial. SABCS 2021 Virtual Meeting, abstract GS1-07.

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