The impact of actual body weight-based chemotherapy dosing and body size on adverse events and outcome in older patients with breast cancer: Results from Cancer and Leukemia Group B (CALGB) trial 49907 (Alliance A151436)

Objective: Actual weight-based (AWB) chemotherapy dosing is recommended for obese patients in the 2012 ASCO Clinical Practice Guideline. CALGB 49907, which utilized ABW-based adjuvant chemotherapy dosing, was a phase 3 trial in women age ≥ 65 years with early stage breast cancer, providing the opportunity to examine impact of such dosing on toxicities and outcome in older patients with breast cancer. Materials and Methods: Adverse event data were available for 615 of 633 enrolled patients. Objectives were to assess grade ≥ 3 hematologic/non-hematologic toxicities by treatment arm, age, study entry BSA/BMI, and relapse-free (RFS) and overall survival (OS) by BSA/BMI. Results: The 615 patients were sub-grouped by BSA (quartiles) and standard BMI categories, with BMI underweight/normal weight categories combined. Overall, grade ≥ 3 non-hematologic and hematologic toxicities occurred in 39.8% and 28.3% of patients, respectively. There were no significant differences in grade ≥ 3 toxicities among BSA quartiles. However, more grade ≥ 3 hematologic toxicities occurred in the underweight/normal weight BMI subgroup compared to overweight/obese subgroups (p = 0.048). Type of chemotherapy and age had no impact on toxicity occurrence by BSA/BMI categories. RFS was superior in the 25th–50th BSA percentile patients in univariate analysis (p = 0.042), as was OS in both univariate and multivariate analyses (p = 0.007, p = 0.009, respectively). No differences in RFS or OS were found by BMI categories. Conclusion: Obesity was not correlated with adverse relapse or survival outcome, and grade ≥ 3 toxicities were not greater with ABW-based dosing. This supports safety and efficacy of ABW-based dosing as per the 2012 ASCO clinical practice guideline. ClinicalTrials.gov Identifier: NCT00024102 (49907).