Carboplatin dose capping affects pCR rate in HER2-positive breast cancer patients treated with neoadjuvant Docetaxel, Carboplatin, Trastuzumab, Pertuzumab (TCHP)

Abstract

Abstract Purpose Estimated glomerular filtration rate (eGFR) is commonly used to calculate carboplatin doses and capping the eGFR may be used to reduce the risk of excessive dosing and toxicity. We sought to retrospectively examine the impact of our carboplatin guidelines on pathological complete response rates (pCR) and toxicity in women with HER2+ breast cancer receiving neoadjuvant docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP). Methods The delivered area under the curve (dAUC) was calculated [(actual carboplatin dose at cycle 1 ÷ dose calculated with uncapped/unbanded eGFR) × 6] and dichotomized at the median value. The impact of this and other clinical factors on pCR rate, dose intensity (DI) and toxicity was assessed. Results 124 eligible patients were identified of whom 63.7% (79/124) achieved pCR. The median dAUC at cycle 1 was 5.75 mg × ml/min. Those with lower dAUC were more frequently younger and overweight/obese. Patients with lower dAUC had significantly inferior pCR rates of 54.8% (34/62) vs 72.6% (45/62), respectively (p = 0.040). Similar results were seen in the ER+ subgroup; 45.2% (19/42) vs 68.3% (28/41), p = 0.037%, whereas no significant difference was seen among ER- patients; 75.0% (15/20) vs 81.0% (17/21), p = 0.72. DI and toxicity were comparable between the two dAUC groups. Conclusions The overall pCR rate was high in patients with HER2+ breast cancer receiving the TCHP regimen; however, carboplatin dose capping resulted in inferior pCR rates, particularly in the ER+ subgroup. To ensure optimal dosing, isotopic measurement of renal function is warranted in patients who would otherwise have their eGFR and dose capped.