KEY TAKEAWAYS
- The PALLAS, phase 3 clinical trial, investigated the correlation between BMI and patients’ effectiveness and adverse event profile of palbociclib.
- The study’s primary aim was to examine whether BMI affects the efficacy and safety of palbociclib in combination with endocrine therapy.
- Patients were classified into underweight, normal weight, overweight, and obese categories based on their BMI, chi-squared tests, and Fine and Gray models.
- The study found a significant decrease in the occurrence and severity of neutropenia in overweight and obese patients compared to those with normal weight.
- Neutropenia was identified as the primary toxicity resulting in treatment discontinuation in patients with palbociclib.
- Out of 5,698 patients, 36.5% had a normal weight, 31.9% were overweight, and 30.4% were obese at baseline assessment.
The impact of Body Mass Index (BMI) on breast cancer risk and prognosis is significant. There have been divergent findings reported in the literature regarding the utility of BMI as a prognostic indicator for the efficacy of endocrine therapy. The standard-of-care treatments for metastatic hormone receptor-positive breast cancer involve the use of CDK4/6 inhibitors (CDK4/6i) in combination with endocrine treatment (ET). Unlike cytotoxic chemotherapy, CDK4/6 inhibitors are administered at a standardized dosage, regardless of the patient’s BMI or weight. In the early breast cancer setting, the PALLAS trial compared the combination of palbociclib, a CDK4/6 inhibitor, and adjuvant ET with ET alone. This study examined the correlation between body mass index (BMI) and the effectiveness and adverse event profile of palbociclib (P) in the PALLAS clinical trial.
In this predetermined examination, individuals enrolled in PALLAS were classified based on their body mass index (BMI) as follows: those who were underweight (BMI <18.5 kg/m2), those who had a normal weight (BMI 18.5-24.9 kg/m2), those who were overweight (BMI 25-29.9 kg/m2), and those who were obese (³30 kg/m2). Chi-squared tests were utilized to evaluate variations in adverse events. The duration until the premature cessation of P was evaluated utilizing Fine and Gray models for competing risks. Cox models were used to examine the correlation between body mass index (BMI) classification and the duration of invasive disease-free survival (iDFS).
Out of the entire cohort of 5698 patients that were considered for this study, 68 individuals (1.2%) were classified as being underweight, 2082 (36.5%) were categorized as having a normal weight, 1818 (31.9%) were classified as being overweight, and 1730 (30.4%) were classified as being obese at the baseline assessment. Distinct variations in the incidence of all-grade neutropenia were noted among patients of normal weight, overweight, and obese categories in terms of total (88.5%, 85.7%, and 74.7%), along with grade 3 (64.1%, 62.0%, and 43.9%) and grade 4 neutropenia (7.0%, 3.6%, and 2.0%), respectively. The incidence of neutropenia was found to be lower in overweight and obese patients, which resulted in a significantly lower rate of treatment discontinuation over time compared to patients with normal weight. The hazard ratio for overweight versus normal weight was 0.73 with a confidence interval of 0.63-0.84 and a P< 0.0001. Similarly, the hazard ratio for obese versus normal weight was 0.65 with a confidence interval of 0.56-0.75 and a P<0.0001. Among patients who received treatment with P, neutropenia was identified as the primary toxicity that resulted in discontinuation of treatment in 21.1% of patients with normal weight, 14.0% of patients who were overweight, and 5.9% of patients who were obese. Notwithstanding these observations, there was no statistically noteworthy enhancement in invasive disease-free survival (iDFS) upon the incorporation of P to endocrine therapy (ET) across all weight classifications (normal weight HR 0.84 CI 0.63-1.12, overweight HR 1.10 CI 0.82-1.49 and obese HR 0.95 CI 0.69-1.30).
The premeditated evaluation of results based on BMI in the PALLAS clinical trial revealed a noteworthy decrease in the occurrence and severity of neutropenia in overweight and obese patients in comparison to those with normal weight. This leads to a significant reduction in the rate of discontinuation of treatment. Nevertheless, no discernible variation in iDFS outcomes based on BMI was noted. Further long-term follow-up will be conducted to evaluate if BMI ultimately affects the outcome.
Source: https://meetings.asco.org/abstracts-presentations/209134
Clinical Trail: https://clinicaltrials.gov/ct2/show/NCT02513394
Georg Pfeiler, Dominik Hlauschek, Erica L. Mayer, Christine Deutschmann, Stephanie Kacerovsky-Strobl, Miguel Martin, Jane Lowe Meisel, Nicholas Zdenkowski, Sibylle Loibl, Marija Balic, Haeseong Park, Aleix Prat, Claudine Isaacs, Jana Machacek-Link, Celine Schurmans, Kathy Puyana Theall, Christian Fesl, Amylou C. Dueck, Angela DeMichele, Michael Gnant/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/J Clin Oncol 40, 2022 (suppl 16; abstr 518)DOI10.1200/JCO.2022.40.16_suppl.518
