Status: Treatment Phase & Follow-up

PALbociclib CoLlaborative Adjuvant Study: A randomized phase III trial of palbociclib with standard adjuvant endocrine therapy versus standard adjuvant endocrine therapy alone for hormone receptor positive (HR+) / human epidermal growth factor receptor 2 (HER2)-negative early breast cancer

Coordinating Investigator: Michael Gnant (Vienna)
Start of study: 09/2015 (global), 10/2015 (national)
Sample size: 5.600
Sponsor: ABCSG (20 countries), AFT (US)


Description and status:

The adjuvant early breast cancer study ABCSG 42 / PALLAS (AFT-05 / BIG14-03) is ABCSG’s largest trial and a successful cooperation between academic and industry partners. The trial is conducted in 21 countries and ABCSG acts as legal sponsor in cooperation with the BIG network, for all 20 non-US countries involved. Recruitment was closed in late 2018, enrolling over 5.700 patients worldwide. The analysis of the scheduled second interim analysis of PALLAS showed that the addition of palbociclib to standard endocrine therapy was unlikely to provide the expected benefit to patients (published in Lancet Oncology: Mayer E et al., 2021). Importantly, however, no safety concerns were raised by this analysis. This result led the Independent Data Monitoring Committee (IDMC) to recommending to prematurely end the treatment phase of PALLAS. Upon the subsequent Steering Committee (SC) decision, all remaining active PALLAS patients were moved to the follow-up phase of the trial in June 2020. The follow-up phase is being conducted as per protocol until 2028 and biosample collection during follow-up for the translational research program Trans-PALLAS was even extended with the last implemented protocol amendment to collect additional blood samples 7- and 10-years post-randomization, respectively. The event size pre-defined to trigger the final analysis was reached in late 2020, with 469 documented invasive Disease-Free Survival (iDFS) events. That analysis dataset was presented prominently in an oral presentation at SABCS 2021 and in a parallel publication released by the Journal of Clinical Oncology. Additionally, the date of awareness for the pre-defined, event-driven stage IIA update analysis was reached in late 2021 and that data set was subsequently presented at the virtual ASCO monthly plenary session in October 2022.

Keeping as many PALLAS patients in the extensive, ongoing follow-up phase of the study is a main aim of the current study phase. This will continue to ensure patient safety through close long-term monitoring and is continuously generating a valuable data resource that will be used to address questions aimed at understanding and developing treatment of early breast cancer in the future. The first Trans-PALLAS projects, as part of the ambitious translational program associated with the PALLAS trial, are well under way. RNA sequencing of all available baseline tumor samples is completed, and the generated data resource will be made available for future scientific projects. Additionally, 18 exploratory clinical or translational research proposals were endorsed by the PALLAS steering committee after being submitted through the first PALLAS harmonized, international research call for proposals. These projects will be conducted in close collaboration between the researchers and both sponsors and will keep all global teams engaged with this cohort and related research questions for many more years to come.

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