Despite Positive Outcomes, Addition of Palbociclib to Adjuvant Endocrine Therapy Did Not Improve iDFS in Stage IIA ER+ Breast Cancer Subgroup


After a median of 50 months of follow-up, palbociclib plus adjuvant endocrine therapy did not improve invasive disease-free survival in a subgroup of patients with stage IIA estrogen receptor–positive breast cancer

Although patients experienced excellent outcomes across both cohorts, palbociclib (Ibrance) and adjuvant endocrine therapy did not improve invasive disease-free survival (iDFS) over endocrine therapy alone in the subgroup of patients with stage IIA estrogen receptor–positive breast cancer treated on the phase 3 PALLAS trial (NCT02513394). Evaluation of biomarkers may help to identify patients who require escalation of adjuvant therapy, investigators stated.

The 4-year iDFS rate was 92.9% in the palbociclib/endocrine therapy arm vs 92.1% in the endocrine therapy alone arm (HR, 0.75; 95% CI, 0.48-1.19; log-rank P = .23). Moreover, investigators reported no difference in distant recurrence, second primary invasive cancers of non-breast origin, locoregional recurrence, contralateral recurrence, or death without recurrence events between arms. No differential iDFS benefit was observed regarding histologic grade, chemotherapy receipt, age, and anatomic clinical risk. No benefit was observed with the addition of palbociclib at 2 years with a median follow-up of 43 months based on stage. Those with stage IIB/III disease had a 4-year iDFS rate of 85.3% following treatment with palbociclib and endocrine therapy vs 83.6% with endocrine therapy alone (HR, 0.91; 95% CI, 0.77-1.07; log-rank P = .24).

To enroll on the study, patients were required to have stage II/III hormone receptor–positive, HER2-negative breast cancer. They also needed to have undergone prior surgery with or without chemotherapy and radiotherapy. Patients were within 12 months of their diagnosis and within 6 months of beginning endocrine therapy. Formalin-fixed paraffin-embedded tumor blocks were submitted to a biorepository.

Patients were randomly assigned 1:1 and stratified based on stage, chemotherapy, age, and geographic region. Those in the experimental arm received palbociclib for 2 years at 125 mg in a 3-weeks-on, 1-week-off schedule plus endocrine therapy, and the experimental arm received the same endocrine therapy backbone. A total of 5600 patients enrolled on the study and 1010 were included in the stage IIA intent-to-treat subgroup.

The primary study end point was iDFS, with key secondary end points including iDFS excluding secondary cancers of non-breast origin, distant recurrence-free survival (DRFS), locoregional recurrence-free survival (LRFS), overall survival (OS), and safety. Translational end points consisted of biomarkers, adherence, and quality of life.

The median patient age in the stage IIA group was 55 years in the palbociclib group vs 53 years in the endocrine therapy group. A total of 56.1% and 55.0% of patients in both respective groups previously received chemotherapy.

Other findings from the study indicated that the invasive breast cancer-free survival rate was 94.8% in the experimental arm vs 94.2% in the control arm (HR, 0.80; 95% CI, 0.47- 1.36). The LRFS rate was 98.1% and 98.2% in each respective arm (HR, 0.84; 95% CI, 0.35-2.00) and the DRFS rate was 95.3% and 95.2%, respectively (HR, 0.92; 95% CI, 0.52-1.65). Additionally, the 4-year OS rate was 97.7% among those treated with palbociclib and endocrine therapy vs 98.1% for endocrine therapy alone (HR, 1.28; 95% CI, 0.57-2.86).


DeMichele A, Dueck A, Hlauschek, et al. Adjuvant palbociclib for ER+ breast cancer (PALLAS trial (ABCSG-42/AFT-05/PrE0109/BIG-14-13): a preplanned analysis of the stage IIA cohort. J Clin Oncol. 2022;40(36):390216. doi:10.1200/JCO.2022.40.36_suppl.390216

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