PALLAS Trial: Adjuvant Palbociclib OS and Post-Recurrence Outcomes

In the phase 3 PALLAS study (NCT02513394), long-term data revealed no difference in overall survival (OS) when comparing adjuvant palbociclib (Ibrance) plus standard adjuvant endocrine therapy (ET) against ET alone for patients with stage II or III hormone receptor–positive, HER2-negative breast cancer, following adjustment for clinical factors and post-recurrence treatment.¹

Findings presented at the 2025 San Antonio Breast Cancer Symposium showed that patients in the palbociclib arm were half as likely to receive a CDK4/6 inhibitor in the metastatic setting compared with those treated with ET alone after adjusting for factors like geographic region, distant-recurrence free interval, age, and distant recurrence site (HR, 0.50; 95% CI, 0.41-0.62; P = <.0001).

The unadjusted post-recurrence OS was 22.6 months in the palbociclib arm (n = 377) vs 27.9 months in the ET alone arm (n = 404; HR, 1.21; 95% CI 1.01-1.46; P = 0.04). When adjusting for clinical factors and post-recurrence treatment, the OS difference was comparable (HR,1.05; 95% CI, 0.86-1.29; P =.64).

“The PALLAS study OS analysis highlights the importance of detailed long-term follow-up and post-recurrence survival analyses in CDK4/6 inhibitor trials,” lead study author Angela DeMichele, MD, MSCE, said in a presentation of the data.

DeMichele is the co-leader of both the Breast Cancer Research Program and the 2-PREVENT Breast Cancer Translational Center of Excellence, as well as the Mariann T. and Robert J. Macdonald Professor in Breast Cancer Care Excellence at the Penn Medicine Rena Rowan Breast Center in Philadelphia.

PALLAS Efficacy Data

Findings showed that patients who received standard adjuvant ET plus palbociclib (n = 2880) experienced 5- and 7-year invasive disease–free survival (iDFS) rates of 84.3% and 79.3%, respectively, compared with respective rates of 82.4% and 76.9% in patients who received adjuvant ET alone (n = 2868; HR, 0.90; 95% CI, 0.80-1.01). In terms of distant relapse–free survival (DRFS), patients in the palbociclib arm achieved 5- and 7-year rates of 87.3% and 82.9%, respectively, whereas patients in the ET alone arm had respective rates of 85.9% and 81.3% (HR, 0.92; 95% CI, 0.81-1.05). For OS, rates were 92.7% at 5 years and 89.0% at 7 years in the experimental arm compared with 92.9% and 88.3%, respectively, in the control arm (HR, 0.99; 95% CI, 0.84-1.17).

Study Design and Rationale

Investigators sought to evaluate whether the addition of palbociclib would achieve the same improvements in iDFS in the adjuvant setting as other CDK4/6 inhibitors, such as abemaciclib (Verzenio), which produced a significant OS improvement in hormone receptor–positive/HER2-negative breast cancer in the phase 3 monarchE trial (NCT03155997).²

PALLAS was a multicenter, prospective, international, randomized, open-label trial that enrolled patients at least 18 years of age with hormone receptor–positive, HER2-negative, stage II or III early invasive breast cancer.³ Patients were required to have an ECOG performance status of 0 or 1, and adequate definitive surgery for their current malignancy.

Patients were randomly assigned to receive palbociclib at 125 mg once per day on a 3-weeks-on/1-week-off schedule for up to 2 years, plus standard ET for up to 5 years, or adjuvant ET alone for up to 5 years.

The trial’s primary end point was iDFS. OS was the preplanned secondary endpoint, while other secondary end points included DRFS, OS, and locoregional survival.

Additional Findings

Findings also showed patients in the palbociclib plus ET arm experienced slightly less DRFS compared with patients in the ET alone arm (377 vs 401). Moreover, the palbociclib plus ET arm yielded less cases of bones as first site of distant recurrence (38% vs 45%), in addition to more cases of visceral recurrences as first site of distance recurrence (46% vs 36%), compared with the ET alone arm.

ET as first treatment initiated after recurrence was less common in the palbociclib plus ET arm (59%) vs the ET alone arm (69%). CDK4/6 inhibitors followed the same trend but with a significant difference in respective rates of 41% and 66%. However, chemotherapy or antibody-drug conjugates were more common for the palbociclib plus ET arm (51%) vs the ET alone arm (45%).

REFERENCES

1. DeMichele A, Dueck A, Gnant M, et al. Adjuvant palbociclib for ER+ breast cancer (PALLAS trial ABCSG-42/AFT-05/PrE0109/BIG-14-13): post-recurrence treatment and overall survival. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract RF7-07.

2. Mayer EL, Hlauschek D, Gnant M, et al. Palbociclib with adjuvant endocrine therapy in early breast cancer: 5-year follow-up analysis of the global multicenter, open-label, randomized phase III PALLAS trial (ABCSG-42/AFT-05/PrE0109/BIG-14-13). Ann Oncol. Published online October 17, 2025. doi:10.1016/j.annonc.2025.10.003

3. Johnston S, Martin M, O’Shaughnessy J, Shahir A, et al. Overall survival with abemaciclib in early breast cancer. Ann Oncol. Published online October 17, 2025. doi:10.1016/j.annonc.2025.10.005

4. PALbociclib coLlaborative adjuvant study (PALLAS). ClinicalTrials.gov. Updated June 11, 2025. Accessed December 11, 2025. https://clinicaltrials.gov/study/NCT02513394