PALbociclib CoLlaborative Adjuvant Study

This is a prospective, two arm, international, multicenter, randomized, open-label Phase III study evaluating the addition of 2 years of palbociclib to standard adjuvant endocrine therapy for patients with HR+ / HER2- early breast cancer (EBC). The purpose of the PALLAS study is to determine whether the addition of palbociclib to adjuvant endocrine therapy will improve outcomes over endocrine therapy alone for HR+/HER2- early breast cancer. Assessment of a variety of correlative analysis, including evaluation of the effect of palbociclib in genomically defined tumor subgroups, is planned.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Signed informed consent prior to study specific procedures.
* Age ≥18 years (or per national guidelines).
* Pre- and postmenopausal women or men with Stage II (Stage IIA limited to max. 1000 patients) or Stage III early invasive breast cancer
* Patients with multicentric and/or multifocal and/or bilateral early invasive breast cancer are eligible if all histopathologically examined tumors meet pathologic criteria for ER+ and/or PR+ and HER2-.
* Patients must have histologically confirmed ER+ and/or PR+, HER2-, early invasive breast cancer.
* Patients must have undergone adequate (definitive) breast surgery for the current malignancy.

FFPE tumor tissue block must be confirmed to be received at the central sample repository prior to randomization.

* ECOG performance status 0-1.
* Patients must be able and willing to swallow and retain oral medication.
* Serum or urine pregnancy test must be negative in premenopausal women within 14 days of randomization, or in women with amenorrhea of less than 12 months at time of randomization.
* Patients who received neo/adjuvant therapy must be after last dose of chemotherapy and/or biologic therapy and must have sufficient resolution of side effects.
* Patients who received breast/axilla/post-mastectomy chest wall radiotherapy must be after last dose of radiotherapy and must have sufficient resolution of side effects.
* Patients must have sufficient resolution of any surgical side effects (no active wound healing complications).

-Patients must either be initiating or have already started adjuvant hormonal treatment. -

* Patients who already received neo/adjuvant endocrine therapy are eligible as long as they are enrolled within 12 months of initial histological diagnosis and after completing no more than 6 months of adjuvant endocrine therapy.
* Absolute neutrophil count ≥ 1,500/µL
* Platelets ≥ 100,000/ mm3
* Hemoglobin ≥ 10g/dL
* Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with documented Gilbert's Syndrome.
* Aspartate amino transferase (AST or SGOT) and alanine amino transferase (ALT or SGPT) ≤ 1.5 × institutional ULN.
* Serum creatinine below the upper limit of the institutional normal range (ULN) or creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN.

Exclusion Criteria:

* Concurrent therapy with other Investigational Products.
* Prior therapy with any CDK inhibitor.
* Patients with Stage I or IV breast cancer are not eligible.
* History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib.
* Patients receiving any medications or substances that are potent inhibitors or inducers of
* CYP3A isoenzymes within 7 days of randomization.
* Uncontrolled intercurrent illness that would limit compliance with study requirements.
* Pregnant women, or women of childbearing potential without a negative pregnancy test within 14 days prior to randomization.
* Patients with a history of any malignancy are ineligible
* Patients who previously received endocrine therapy within 5 years prior to diagnosis of the current malignancy.
* Patients on antiretroviral therapy.
* Patients with clinically significant history of any chronic liver disease.
* Patients receiving concurrent exogenous hormone therapy (topical vaginal estrogen therapy is allowable).

• DERIVEDShinn E, Zahrieh D, DeMichele A, Zdenkowski N, Lemieux J, Mao J, Bjelic-Radisic V, Naughton MJ, Pfeiler G, Gelmon K, Balko JM, Egle D, Zoppoli G, Traina T, Jimenez MM, Novoa SA, Haddad T, Chan A, Ring A, Wolff A, Symmans WF, Ponce Lorenzo J, Sabanathan D, Burstein HJ, Nowecki ZI, Pristauz-Telsnigg G, Brufsky A, Bellet-Ezquerra M, Foukakis T, Novik Y, Rubovszky G, Singer CF, Muehlbacher K, Filho OM, Goulioti T, Law E, Partridge AH, Carey LA, Zoroufy A, Hlauschek D, Fesl C, Mayer EL, Gnant M. Impact of adding palbociclib on treatment adherence to ongoing adjuvant endocrine treatment in the global randomized PALLAS randomized trial in patients with early breast cancer. Breast Cancer Res Treat. 2025 Jun;211(2):385-397. doi: 10.1007/s10549-025-07653-2. Epub 2025 Mar 27. PMID 40140172
• DERIVEDDeMichele A, Dueck AC, Hlauschek D, Martin M, Burstein H, Pfeiler G, Zdenkowski N, Wolff A, Bellet-Ezquerra M, Winer E, Balic M, Miller K, Colleoni M, Lake D, Rubovsky G, Cameron D, Balko J, Singer CF, Nowecki Z, Iwata H, Wolmark N, Parraga KA, Rugo H, Steger GG, Traina T, Werutsky G, Czajkowska D, Metzger O, El-Abed S, Theall KP, Lu RD, O'Brien P, Fesl C, Mayer E, Gnant M. Outcomes in stage IIA versus stage IIB/III in the PALLAS trial [ABCSG-42/AFT-05/PrE0109/BIG-14-13]). Breast Cancer Res. 2025 Jan 23;27(1):12. doi: 10.1186/s13058-024-01941-3. PMID 39849600
• DERIVEDPfeiler G, Hlauschek D, Mayer EL, Deutschmann C, Kacerovsky-Strobl S, Martin M, Meisel JL, Zdenkowski N, Loibl S, Balic M, Park H, Prat A, Isaacs C, Bajetta E, Balko JM, Bellet-Ezquerra M, Bliss J, Burstein H, Cardoso F, Fohler H, Foukakis T, Gelmon KA, Goetz M, Haddad TC, Iwata H, Jassem J, Lee SC, Linderholm B, Los M, Mamounas EP, Miller KD, Morris PG, Munzone E, Gal-Yam EN, Ring A, Shepherd L, Singer C, Thomssen C, Tseng LM, Valagussa P, Winer EP, Wolff AC, Zoppoli G, Machacek-Link J, Schurmans C, Huang X, Gauthier E, Fesl C, Dueck AC, DeMichele A, Gnant M; PALLAS Groups and Investigators. Impact of BMI in Patients With Early Hormone Receptor-Positive Breast Cancer Receiving Endocrine Therapy With or Without Palbociclib in the PALLAS Trial. J Clin Oncol. 2023 Nov 20;41(33):5118-5130. doi: 10.1200/JCO.23.00126. Epub 2023 Aug 9. PMID 37556775
• DERIVEDMayer EL, Fesl C, Hlauschek D, Garcia-Estevez L, Burstein HJ, Zdenkowski N, Wette V, Miller KD, Balic M, Mayer IA, Cameron D, Winer EP, Ponce Lorenzo JJ, Lake D, Pristauz-Telsnigg G, Haddad TC, Shepherd L, Iwata H, Goetz M, Cardoso F, Traina TA, Sabanathan D, Breitenstein U, Ackerl K, Metzger Filho O, Zehetner K, Solomon K, El-Abed S, Theall KP, Lu DR, Dueck A, Gnant M, DeMichele A. Treatment Exposure and Discontinuation in the PALbociclib CoLlaborative Adjuvant Study of Palbociclib With Adjuvant Endocrine Therapy for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer (PALLAS/AFT-05/ABCSG-42/BIG-14-03). J Clin Oncol. 2022 Feb 10;40(5):449-458. doi: 10.1200/JCO.21.01918. Epub 2022 Jan 7.