Update on PALLAS triaI evaluating adjuvant palbociclib for early breast cancer

The Austrian Breast & Colorectal Cancer Study Group (ABCSG), Alliance Foundation Trials (AFT), the Breast International Group (BIG), PrECOG, LLC, the German Breast Group, and the NSABP Foundation today announced that the independent Data Monitoring Committee (IDMC) for the global Phase 3 early breast cancer PALbociclib CoLlaborative Adjuvant Study (PALLAS) trial determined that the study is unlikely to show a statistically significant improvement in the primary endpoint of invasive disease-free survival (iDFS) following a preplanned interim analysis. No new safety signals were observed in patients receiving palbociclib, which has been proven effective in advanced breast cancer. PALLAS patients in the active phase of the trial will be counselled/instructed by their physicians. All patients will move to protocol-defined extended follow-up. Long-term follow up of patient outcomes will proceed as planned.

PALLAS study design and outcomes

The PALLAS trial is a randomized (1:1), prospective, international, multi-center, open-label Phase 3 study comparing the combination of at least five years of standard adjuvant endocrine therapy along with two years of palbociclib (IBRANCE^®, manufactured by Pfizer) treatment to at least five years of standard adjuvant endocrine therapy (NCT02513394). The study population is pre- and postmenopausal women or men with HR+, HER2- early invasive (Stage 2 and Stage 3) breast cancer, including those at moderate to high risk of recurrence. The study medication is an oral inhibitor of CDK 4 and 6, which are key regulators of the cell cycle. It is currently approved globally for the treatment of patients with metastatic HR+/HER2- breast cancer. The primary study aim was to investigate whether the addition of palbociclib to endocrine therapy significantly improved invasive disease-free survival (iDFS; i.e. reduced the chance of the cancer coming back, or of dying or getting another cancer) compared to standard of care endocrine therapy alone. At the second interim analysis, as reported to the IDMC, the futility boundary was crossed indicating a low probability for meeting the primary endpoint, which led to the Steering Committee's decision.

There remains a great need to improve outcomes for patients with HR+ breast cancer. Our collaborative academic group will continue to closely follow our PALLAS patients and hope to learn from the PALLAS dataset and correlative science how best to improve outcomes in this population. Despite this futility result, the PALLAS trial represents a remarkable collaboration between academic and industry partners, and we hope can serve as a model of cooperative trial conduct."

Erica Mayer, M.D., M.P.H., Senior Physician, Breast Oncology Center, Dana-Farber Cancer Institute, Harvard Medical School, and global PALLAS trial Chair

Global trial Co-Chair Professor Michael Gnant, MD, FACS, of Medical University of Vienna, Austria, president of ABCSG, pointed out the importance of global academic collaboration: "This has been and will continue to be one of the most successful worldwide collaborations between academic study groups to facilitate such a huge pivotal clinical trial - thousands of physicians, researchers, nurses, and other health care professionals in 21 countries around the globe have worked together for many years to make this. The follow-up of patients will continue for at least 10 years from trial entry and provide many additional insights in how to even better conquer breast cancer in the future. "

Angela DeMichele, MD, MSCE, Professor of Medicine and Epidemiology, Perelman School of Medicine at the University of Pennsylvania and global PALLAS Co-Chair, points out another important outcome of the PALLAS study, and describes its potential for further research: "One critically important achievement of PALLAS was the mandatory tissue block collection at the beginning of this enterprise. These samples, along with serially collected blood samples, provide an enormous treasure of opportunities for researchers worldwide to interrogate mechanisms of disease and treatment in numerous translational science projects. Ultimately, this will greatly enhance our understanding of breast cancer, and shed light on the findings of the PALLAS trial."

Health authorities, trial investigators, and patients are being notified of the interim findings. The detailed finding from the PALLAS study will be shared with the scientific community at an upcoming major medical congress.

Academically-led global collaboration

The PALLAS trial is being conducted collaboratively by several academic-based global research groups. PALLAS is co-sponsored by the Austrian Breast & Colorectal Cancer Study Group (ABCSG) and Alliance Foundation Trials (AFT) as part of a clinical research collaboration with Pfizer (providing study drug and funding) and other study groups, including PrECOG, LLC; NSABP Foundation Inc; and the Breast International Group (BIG). This targeted collaboration between academia and industry is allowing the independent generation of clinical data whilst providing a unique public-private research partnership aimed at bringing more innovative cancer treatments to patients in more efficient ways.

More than 400 participating clinical sites in 21 countries enrolled a total of 5,796 patients. The study opened in August 2015. The global recruitment aim was met on schedule, on November 30, 2018, displaying the well-concerted interplay of participating academic groups and their profound experience in clinical research.