Why the study?
In overweight patients, GFR is more likely overestimated by the Cockcroft-Gault formula, potentially resulting in carboplatin overdosing that could affect treatment response.
Does BMI affect overall survival and progression-free survival in stage-IV NSCLC patients treated with first-line carboplatin-based chemotherapy?
Cohort (n=493)
Yes
Does BMI affect overall survival and progression-free survival in stage-IV NSCLC patients treated with first-line carboplatin-based chemotherapy?
Hazard Ratio: 0.72 (95% CI 0.59–0.89)
In stage-IV NSCLC patients receiving first-line carboplatin, being overweight is associated with improved survival, whereas obesity increases the risk of severe thrombocytopenia without survival benefit.
Should not yet guide BMI-based carboplatin dosing in NSCLC; hypothesis-generating for obesity paradox in lung cancer.
Carboplatin is an anticancer drug used for treatment of various types of cancer including non-small cell lung cancer (NSCLC). Dosing is based on estimated glomerular filtration rate (GFR) using the Cockcroft-Gault formula. In overweight patients, the GFR is more likely overestimated, resulting in a potentially overdose of carboplatin affecting treatment response. This study investigated the association of body mass index (BMI) on overall survival (OS) and progression-free survival (PFS) in stage-IV NSCLC patients treated with first-line carboplatin-based chemotherapy. Secondary safety endpoints were thrombocytopenia and toxicity-related hospitalizations. This was a retrospective multicenter cohort study. Patients were categorized according to BMI<25.0 kg/m2 (normal weight and reference), 25.0-29.9 kg/m2 (overweight) or ≥30.0 kg/m2 (obese). For survival analyses adjusted hazard ratios [aHR] were calculated using multivariate Cox regression analysis. Secondary outcomes were analyzed using multivariate logistic regression providing adjusted odd ratios [aOR]. Overweight patients (n=174) had a significantly better OS (aHR=0.72, 95%-CI:0.59-0.89) and PFS (aHR=0.74, 95%-CI:0.61-0.90) compared to normal weight patients (n=268). OS nor PFS were different in obese (n=51) compared to normal weight patients. However, obesity was associated with significantly higher incidences of thrombocytopenia grade ≥3 (aOR=3.47, 95%-CI:1.75-6.90). This study shows a significantly longer survival for overweight compared to normal weight patients. Obese patients have an increased risk for grade ≥3 thrombocytopenia without a difference in survival following carboplatin-based chemotherapy. The implications for clinical practice are to use the Cockcroft-Gault formula with caution in patients with BMI≥30.0 kg/m2, and to verify calculated dosing of carboplatin for appropriateness.
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Kicken et al. (2022) conducted a cohort in Stage-IV non-small cell lung cancer (NSCLC) (n=493). Overweight (BMI 25.0-29.9 kg/m2) vs. Normal weight (BMI <25.0 kg/m2) was evaluated on Overall survival (OS) (aHR 0.72, 95% CI 0.59-0.89).
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