Impact of BMI in Patients With Early Hormone Receptor–Positive Breast Cancer Receiving Endocrine Therapy With or Without Palbociclib in the PALLAS Trial
Authors: Pfeiler Georg , Hlauschek Dominik , Mayer Erica L. , Deutschmann Christine , Kacerovsky-Strobl Stephanie , Martin Miguel , Meisel Jane Lowe , Zdenkowski Nicholas , Loibl Sibylle , Balic Marija , Park Haeseong , Prat Aleix , Isaacs Claudine , Bajetta Emilio , Balko Justin M. , Bellet-Ezquerra Merixtell , Bliss Judith , Burstein Harold , Cardoso Fatima , Fohler Hannes , Foukakis Theodoros , Gelmon Karen A. , Goetz Matthew , Haddad Tufia C. , Iwata Hiroji , Jassem Jacek , Lee Soo-Chin , Linderholm Barbro , Los Maartje , Mamounas Eleftherios P. , Miller Kathy D. , Morris Patrick G. , Munzone Elisabetta , Gal-Yam Einav Nili , Ring Alistair , Shepherd Lois , Singer Christian , Thomssen Christoph , Tseng Ling-Ming , Valagussa Pinuccia , Winer Eric P. , Wolff Antonio C. , Zoppoli Gabriele , Machacek-Link Jana , Schurmans Celine , Huang Xin , Gauthier Eric , Fesl Christian , Dueck Amylou C. , DeMichele Angela , Gnant Michael ,   on behalf of the PALLAS Groups and Investigators, Cameron David , El-Abed Sarra , Rugo Hope S. , Steger Guenther G. , Traina Tiffany , Werutsky Gustavo , Wolmark Norman 
Published: August 2023

PURPOSE BMI affects breast cancer risk and prognosis. In contrast to cytotoxic chemotherapy, CDK4/6 inhibitors are given at a fixed dose, irrespective of BMI or weight. This preplanned analysis of the global randomized PALLAS trial investigates the impact of BMI on the side-effect profile, treatment adherence, and efficacy of palbociclib. METHODS Patients were categorized at baseline according to WHO BMI categories. Neutropenia rates were assessed with univariable and multivariable logistic regression. Time to early discontinuation of palbociclib was analyzed with Fine and Gray competing risk models. Unstratified Cox models were used to investigate the association between BMI category and time to invasive disease-free survival (iDFS). 95% CIs were derived. RESULTS Of 5,698 patients included in this analysis, 68 (1.2%) were underweight, 2,082 (36.5%) normal weight, 1,818 (31.9%) overweight, and 1,730 (30.4%) obese at baseline. In the palbociclib arm, higher BMI was associated with a significant decrease in neutropenia (unadjusted odds ratio for 1-unit change, 0.93; 95% CI, 0.91 to 0.94; adjusted for age, race ethnicity, region, chemotherapy use, and Eastern Cooperative Oncology Group at baseline, 0.93; 95% CI, 0.92 to 0.95). This translated into a significant decrease in treatment discontinuation rate with higher BMI (adjusted hazard ratio [HR] for 10-unit change, 0.75; 95% CI, 0.67 to 0.83). There was no significant improvement in iDFS with the addition of palbociclib to ET in any weight category (normal weight HR, 0.84; 95% CI, 0.63 to 1.12; overweight HR, 1.10; 95% CI, 0.82 to 1.49; and obese HR, 0.95; 95% CI, 0.69 to 1.30) in this analysis early in follow-up (31 months). CONCLUSION This preplanned analysis of the PALLAS trial demonstrates a significant impact of BMI on side effects, dose reductions, early treatment discontinuation, and relative dose intensity. Additional long-term follow-up will further evaluate whether BMI ultimately affects outcome.