According to updated 7-year results from the phase 3 PALLAS trial, adding 2 years of adjuvant palbociclib to endocrine therapy did not significantly improve survival outcomes among patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

These findings were presented by Angela DeMichele, MD, University of Pennsylvania, Philadelphia, Pennsylvania, at the 2025 San Antonio Breast Cancer Symposium in San Antonio, Texas.

In this randomized trial, 5796 patients were assigned to receive at least 5 years of endocrine therapy with or without 2 years of palbociclib. The primary end point was invasive disease-free survival (iDFS). Key secondary end points included distant recurrence-free survival (DRFS) and overall survival (OS). Post-recurrence OS was analyzed from the time of first distant recurrence, adjusting for clinicopathologic factors and time-dependent post-recurrence treatments, including CDK4/6 inhibitor or chemotherapy use.

At a median follow-up of 82.7 months, iDFS rates were 76.3% in the endocrine therapy arm and 79.2% in the palbociclib arm (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.80 to 1.01; P = .80). DRFS rates were 81.3% and 82.9%, respectively (HR, 0.92; 95% CI, 0.81 to 1.05; P = .23), and OS rates were 88.3% and 89% (HR, 0.99; 95% CI, 0.84 to 1.17; P = .89). Among the 781 distant recurrences, visceral recurrences occurred in 36% of patients in the endocrine therapy arm and 46% in the palbociclib arm, while non-visceral recurrences occurred in 68% and 61% of patients, respectively (P = .03). Median unadjusted post-recurrence OS was 27.9 months in the endocrine therapy arm and 22.6 months in the palbociclib arm (HR, 1.21; 95% CI, 1.01 to 1.46; P = .04).

Following recurrence, 66% of patients in the endocrine therapy arm received CDK4/6 inhibitor treatment compared with 41% in the palbociclib arm. Time to CDK4/6 inhibitor initiation was significantly shorter in the endocrine therapy arm (P <.001) after adjustment for region, recurrence site, recurrence-free interval, and age. Time to post-progression chemotherapy initiation was significantly longer in the endocrine therapy arm (HR, 1.31; 95% CI, 1.07 to 1.61; P = .01). After adjustment for clinical factors and post-recurrence treatment, OS differences were no longer observed (HR, 1.05; 95% CI, 0.85 to 1.28; P = .65). A 3-month landmark analysis showed similar findings when adjusting for CDK4/6 inhibitor initiation within 3 months of recurrence (unadjusted P = .03; adjusted P = .22).

“Reduced/delayed use of metastatic CDK4/6i after adjuvant [palbociclib] was associated with significantly poorer OS, suggesting that patients who relapse after adjuvant CDK4/6i may still benefit from metastatic CDK4/6i,” concluded Dr DeMichele. “This has implications for optimal treatment in those who relapse after adjuvant CDK4/6i and warrants further study to determine if this is therapy-specific or an overarching biological effect.”

Source: 

DeMichele A, Dueck A, Gnant M, et al. Adjuvant palbociclib for ER+ breast cancer in the PALLAS trial (ABCSG-42/AFT-05/PrE0109/BIG-14-13): Post-recurrence treatment and overall survival. Presented at SABCS 2025. December 9 - 12, 2025. San Antonio, Texas. Abstract RF7-07