UNDERSTANDING HOW BMI COULD IMPROVE BREAST CANCER TREATMENT: PALLAS FOLLOW-UP

Understanding the impact of medication on different body types could help clinicians deliver the best outcomes for breast cancer patients.

New analysis of data from the PALLAS trial (PALbociclib collaborative Adjuvant Study) has shown the need for further research to ensure that patients in specific Body Mass Index categories receive effective doses.

The PALLAS trial, from 2015–18, recruited nearly 5800 participants worldwide to explore whether palbociclib – a cell-cycle inhibitor effective in treating metastatic disease – improved outcomes when added to standard hormone treatment for early-stage HR-positive, HER2 negative breast cancer.

Although PALLAS didn’t produce the patient benefit researchers hoped for, Australian trial chair Dr Nick Zdenkowski says its results will drive investigation for a decade to come.

This follow-up study re-examined PALLAS data to understand the impact of patient BMI, which affects breast cancer risk and prognosis, on trial results.

While 42% of recipients of the study drug stopped taking it before the end of the two-year trial due to side effects like neutropenia (low white blood cell count) and fatigue, overweight and obese patients experienced fewer side effects, suggesting that they were exposed to a lower concentration of the drug.

“Overweight or obese women have a higher risk of developing breast cancer and worse outcomes after diagnosis,” says Dr Zdenkowski. “The cancer is more likely to return if they’ve been treated with curative intent, or they’re likely to have worse outcomes if their disease is advanced.”

“The researchers were concerned that overweight and obese participants might not have been getting enough of the PALLAS study drug and that there might not have been enough of it in their systems to affect the cancer cells.”

The new study found that wasn’t the case and that palbociclib provided no benefit across BMI categories, although Dr Zdenkowski says it wasn’t designed to answer that specific question.

It did, however, highlight the need to consider BMI in treatment planning.

“Given that many overweight and obese people around the world will still receive [palbociclib] in a metastatic setting, are we potentially doing them a disservice by putting them on the standard dose?” asks Dr Zdenkowski.

The new study also confirms PALLAS’s findings that palbociclib provided no benefit for patients with early stage cancer. While disappointing, Dr Zdenkowski says it’s reassurance that the trial was sound.

“We wanted to know if there was truly a lack of benefit, or whether a different study design might have shown a benefit. But that wasn’t the case.”

Publication:
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.

Pfeiler 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.