January 2024 - Georg Pfeiler

Dr. Georg Pfeiler

MedUni Wien RESEARCHER OF THE MONTH January 2024

"Impact of body mass index on treatment and outcomes in patients with early hormone receptor-positive breast cancer receiving endocrine therapy with or without palbociclib in the PALLAS trial", published in Journal of Clinical Oncology, August 2023.

Obesity is a substantial health problem impacting the risk and the course of various diseases, and is increasing worldwide.
The distributional volume of any systemic treatment may be increased in overweight and obese patients, resulting in reduced plasma concentrations of therapeutic agents, including CDK4/6 inhibitors. This pre-planned analysis demonstrates a significant and substantial impact of BMI on overall as well as grade 3 and 4 neutropenia leading to significant differences in dose reductions, early treatment discontinuation and relative dose intensity. With this analysis early in follow up no impact of BMI on the efficacy of palbociclib could be observed.

Our data suggest that palbociclib is either underdosed in overweight and obese patients or overdosed in normal weight patients. An additional long term follow up will further evaluate whether BMI ultimately

impacts outcome.Our data demand to focus on the therapeutic window and the (way of) dosing of oral oncologic agents in general.

Selected Literature

1. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial.
   Gnant M, Pfeiler G, Dubsky PC, Hubalek M, Greil R, Jakesz R, Wette V, Balic M, Haslbauer F, Melbinger E, Bjelic-Radisic V, Artner-Matuschek S, Fitzal F, Marth C, Sevelda P, Mlineritsch B, Steger GG, Manfreda D, Exner R, Egle D, Bergh J, Kainberger F, Talbot S, Warner D, Fesl C, Singer CF; Austrian Breast and Colorectal Cancer Study Group. Lancet. 2015 Aug 1;386(9992):433-43.

2. Impact of body mass index on the efficacy of endocrine therapy in premenopausal patients with breast cancer: an analysis of the prospective ABCSG-12 trial. Pfeiler G, Königsberg R, Fesl C, Mlineritsch B, Stoeger H, Singer CF, Pöstlberger S, Steger GG, Seifert M, Dubsky P, Taucher S, Samonigg H, Bjelic-Radisic V, Greil R, Marth C, Gnant M.J Clin Oncol. 2011 Jul 1;29(19):2653-9.

3. The predictive impact of body mass index on the efficacy of extended adjuvant endocrine treatment with anastrozole in postmenopausal patients with breast cancer: an analysis of the randomised ABCSG-6a trial.
   Gnant M, Pfeiler G, Stöger H, Mlineritsch B, Fitzal F, Balic M, Kwasny W, Seifert M, Stierer M, Dubsky P, Greil R, Steger G, Samonigg H, Fesl C, Jakesz R.Br J Cancer. 2013 Aug 6;109(3):589-96.

4. Impact of body mass index on the efficacy of endocrine therapy in premenopausal patients with breast cancer: an analysis of the prospective ABCSG-12 trial.
   Pfeiler G, Königsberg R, Fesl C, Mlineritsch B, Stoeger H, Singer CF, Pöstlberger S, Steger GG, Seifert M, Dubsky P, Taucher S, Samonigg H, Bjelic-Radisic V, Greil R, Marth C, Gnant M.J Clin Oncol. 2011 Jul 1;29(19):2653-9.

5. Impact of body mass index on estradiol depletion by aromatase inhibitors in postmenopausal women with early breast cancer.
   Pfeiler G, Königsberg R, Hadji P, Fitzal F, Maroske M, Dressel-Ban G, Zellinger J, Exner R, Seifert M, Singer C, Gnant M, Dubsky P.Br J Cancer. 2013 Sep 17;109(6):1522-7.

6. Vaginal estriol to overcome side-effects of aromatase inhibitors in breast cancer patients.
   Pfeiler G, Glatz C, Königsberg R, Geisendorfer T, Fink-Retter A, Kubista E, Singer CF, Seifert M.Climacteric. 2011 Jun;14(3):339-44. doi:

7. Adjuvant denosumab in postmenopausal patients with hormone receptor-positive breast cancer (ABCSG-18): disease-free survival results from a randomised, double-blind, placebo-controlled, phase 3 trial.
   Gnant M, Pfeiler G, Steger GG, Egle D, Greil R, Fitzal F, Wette V, Balic M, Haslbauer F, Melbinger-Zeinitzer E, Bjelic-Radisic V, Jakesz R, Marth C, Sevelda P, Mlineritsch B, Exner R, Fesl C, Frantal S, Singer CF; Austrian Breast and Colorectal Cancer Study Group.Lancet Oncol. 2019 Mar;20(3):339-351.

8. Safety of adjuvant CDK4/6 inhibitors during the COVID-19 pandemic.
   Pfeiler G, DeMichele A, Dueck AC, Fesl C, Gnant M, Mayer EL.Lancet Oncol. 2022 Feb;23(2):195-197.

9. Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03).
   Gnant M, Dueck AC, Frantal S, Martin M, Burstein HJ, Greil R, Fox P, Wolff AC, Chan A, Winer EP, Pfeiler G, Miller KD, Colleoni M, Suga JM, Rubovsky G, Bliss JM, Mayer IA, Singer CF, Nowecki Z, Hahn O, Thomson J, Wolmark N, Amillano K, Rugo HS, Steger GG, Hernando Fernández de Aránguiz B, Haddad TC, Perelló A, Bellet M, Fohler H, Metzger Filho O, Jallitsch-Halper A, Solomon K, Schurmans C, Theall KP, Lu DR, Tenner K, Fesl C, DeMichele A, Mayer EL; PALLAS groups and investigators.J Clin Oncol. 2022 Jan 20;40(3):282-293.