PALLAS Trial Provides New Wisdom for
Early-Stage Breast Cancer Treatment

According to the Australian chair of the recent PALLAS trial, Dr Nick Zdenkowski, much was gained from this study that will influence future trials and treatments.

The PALLAS (Palbociclib Collaborative Adjuvant Study) trial investigated whether palbociclib, a cell cycle inhibitor drug that is highly successful in treating metastatic breast cancer, improves survival outcomes for early-stage, high-risk patients.

The primary 31-month analysis that followed the two-year trial found that adding palbociclib had no benefit over standard hormone therapy treatment alone. “We were a bit surprised as we had high hopes for the study drug,” Dr Zdenkowski says. “However, the additional information obtained means it was not a loss by any means. We will be following these patients for 10 years and there will be much to learn from the ongoing analysis of the patient outcomes and blood and tissue samples collected.”

A feature of the study was the use of extensive patient questionnaires, providing rich detail that researchers hope will inform future treatments. “We know that keeping patients at the centre of their decision-making is associated with high-quality care,” Dr Zdenkowski says. “By asking patients questions rather than relying on doctors’ assessment on what their patients are experiencing, we will be better able to understand quality of life considerations, side effects and why patients may have stopped taking the drug early.”

The trial explored whether the addition of palbociclib to standard hormone therapy treatment improved outcomes for patients with early-stage hormone receptor positive (HR positive), human epidermal growth factor receptor 2 negative (HER2 negative) breast cancer.

PALLAS was a large international trial involving almost 5,800 patients (including 434 Australian patients from 20 participating institutions) willing to participate in long-term follow up and prepared to be randomised, meaning that neither they nor the treating medical team could choose which treatment they received. Approximately half the patients received standard hormone therapy treatment while the remainder received the standard treatment plus palbociclib.

One of the surprises from the PALLAS trial was that almost 42% of patients on the study drug stopped taking it before the end of the two-year period. “The reasons for this included fatigue and feeling unwell in spite of the protocols surrounding dose reduction,” Dr Zdenkowski says. The study protocol allowed for two reductions in dose if the patients experienced side effects including fatigue and neutropenia (low white blood cell count, which, if severe, can increase the risk of infection).

A second research paper looked at the outcomes for patients who stopped taking palbociclib early against those who continued taking it. It found that there was no apparent benefit for people who stayed on the study drug for the whole two years or were exposed to greater than 70 per cent of the intended treatment. Researchers were concerned that the lack of benefit seen in the full study population might have been because some patients either stopped early or were not taking their medication all the time. This second paper offers very important insight, showing that this was not the case, and that the primary results are valid.

“At the 31-month mark, somewhere between 96 and 97 per cent of the entire study patients were alive and more than 90 per cent did not have cancer recurrence,” Dr Zdenkowski says. “For patients with high-risk cancer, they were doing well. This type of cancer can come back years, sometimes decades, down the track. The long-term questionnaire follow up is so important because the responses allow doctors to give patients better information about the future.”

Publication

Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/ AFT-05/BIG-14-03)

Michael Gnant, MD1,2; Amylou C. Dueck, PhD3 ; Sophie Frantal, MSc2 ; Miguel Martin, MD4,5; Hal J. Burstein, MD6 ; Richard Greil, MD7 ; Peter Fox, MBBS8 ; Antonio C. Wolff, MD9 ; Arlene Chan, MMed10; Eric P. Winer, MD6 ; Georg Pfeiler, MD1,11; Kathy D. Miller, MD12; Marco Colleoni, MD13; Jennifer M. Suga, MD14; Gabor Rubovsky, PhD15; Judith M. Bliss, MSc16; Ingrid A. Mayer, MD17; Christian F. Singer, MD1,11; Zbigniew Nowecki, MD18; Olwen Hahn, MD19; Jacqui Thomson, MBBS 20; Norman Wolmark, MD21; Kepa Amillano, MD22; Hope S. Rugo, MD23; Guenther G. Steger, MD1 ; Blanca Hernando Fernandez de Ar ´ anguiz, MD ´ 5,24; Tufia C. Haddad, MD25; Antonia Perello, MD ´ 26; Meritxell Bellet, MD27; Hannes Fohler, MVM2 ; Otto Metzger Filho, MD5,28; Anita Jallitsch-Halper, PhD2 ; Kadine Solomon, BA28; Celine Schurmans, MSc ´ 29; Kathy P. Theall, MD30; Dongrui R. Lu, MS31; Kathleen Tenner, MSc25; Christian Fesl, PhD2; Angela DeMichele, MD32; and Erica L. Mayer, MD, MPH5

on behalf of the PALLAS groups and investigatorsTreatment 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) Erica L. Mayer, MD, MPH1 ; Christian Fesl, PhD2 ; Dominik Hlauschek, MS2 ; Laura Garcia-Estevez, MD3,4; Harold J. Burstein, MD, PhD1 ; Nicholas Zdenkowski, MD, PhD5 ; Viktor Wette, MD6 ; Kathy D. Miller, MD7 ; Marija Balic, MD8 ; Ingrid A. Mayer, MD, MSCI9 ; David Cameron, MD, MSc10; Eric P. Winer, MD1 ; Jose Juan Ponce Lorenzo, MD ´ 4,11; Diana Lake, MD12; Gunda Pristauz-Telsnigg, MD8 ; Tufia C. Haddad, MD13; Lois Shepherd, MDCM14; Hiroji Iwata, MD, PhD15;