In a preplanned analysis of the phase III PALLAS trial reported in the Journal of Clinical Oncology, Pfeiler et al found that higher body mass index (BMI) reduced the risk of neutropenia and treatment discontinuation in patients with early hormone receptor–positive breast cancer receiving adjuvant treatment with the CDK4/6 inhibitor palbociclib plus standard endocrine therapy. BMI had no effect on invasive disease–free survival outcomes for palbociclib plus endocrine therapy vs endocrine therapy alone.
The second interim analysis of the trial showed no invasive disease–free survival benefit with the addition of palbociclib to endocrine therapy.
As noted by the investigators, “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.”
Study Details
In the trial, patients were randomly assigned to receive endocrine therapy for at least 5 years with or without palbociclib at 125 mg once daily (3 weeks on/1 week off) for 2 years. Among 5,698 patients included in the analysis, 68 (1.2%) were affected by underweight, 2,082 (36.5%) had normal weight, 1,818 (31.9%) had overweight, and 1,730 (30.4%) had obesity at baseline.
In the palbociclib group, higher BMI was associated with a significant decrease in the risk of neutropenia (unadjusted odds ratio [OR] for 1-unit change = 0.93, 95% confidence interval [CI] = 0.91–0.94; OR for 1-unit change adjusted for age, race/ethnicity, region, chemotherapy use, and Eastern Cooperative Oncology Group performance status at baseline = 0.93, 95% CI = 0.92–0.95).
Within 6 months of treatment, 52.3% of patients with normal weight had their palbociclib dose reduced to 100 mg once daily compared with 43.4% of those with overweight and 28.9% of those with obesity. Relative average dose intensity was 53.7% in patients with normal weight, compared with 60.6% and 66.1% in patients with overweight and obesity. A significant decrease in treatment discontinuation rate was observed with higher BMI in the palbociclib group (adjusted hazard ratio for 10-unit change = 0.75, 95% CI = 0.67–0.83).
Survival Outcomes
No significant improvement in invasive disease–free survival with the addition of palbociclib to endocrine therapy was observed in any weight category. Hazard ratios were 0.84 (95% CI = 0.63–1.12) for normal weight; 1.10 (95% CI = 0.82–1.49) for overweight; and 0.95 (95% CI = 0.69–1.30) for obesity after follow-up of 31 months.
The investigators concluded: “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.”
Georg Pfeiler, MD, of the Department of Gynecology and Gynecological Oncology, Medical University of Vienna, Austria, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Alliance Foundation Trials, LLC; Pfizer; and others. For full disclosures of the study authors, visit ascopubs.org.
