Dat Le1, Craig Vargo2, Stephanie Collins2, Nicole Williams3, Marilly Palettas4, Michael Berger2. 1. Department of Pharmacy, The Arthur G. James Cancer Hospital and Richard J, Solove Institute at The Ohio State University, 460 W 10th Ave, Columbus, OH, 43210, USA. Dat.Le@osumc.edu. 2. Pharmacy Department, The Stefanie Spielman Comprehensive Breast Center, The James Cancer Hospital and Solove Research Institute at the Ohio State University, Columbus, OH, USA. 3. Division of Medical Oncology, The Ohio State University Wexner Medical Center, The Stefanie Spielman Comprehensive Breast Center, Columbus, OH, USA. 4. Center for Biostatistics, The Ohio State University, Columbus, OH, USA.
Abstract
BACKGROUND: Neoadjuvant chemotherapy is the cornerstone treatment for locally advanced breast cancer. Balancing toxicity and efficacy are a common concern of patients treated with chemotherapy. OBJECTIVE: The objective of this study was to determine the impact of dose intensity on pathologic complete response (pCR) at the time of surgery in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. PATIENTS AND METHODS: A retrospective, single-center review was conducted on patients with HER2+ breast cancer who received neoadjuvant docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP) followed by definitive surgery. RESULTS: A total of 159 patients were included in the analysis; pCR was obtained in 66 patients (42%). There was no statistically significant difference between the mean dose intensity of each of the individual agents in TCHP and pCR rates. The mean overall dose intensity of docetaxel, carboplatin, trastuzumab and pertuzumab was 90.5%, 90.9%, 97.5%, and 93.9%, respectively. Although higher chemotherapy dose intensity (> 85%) was associated with higher pCR rates, no statistically significant difference was found compared with chemotherapy dose intensity < 85%. The TCHP regimen was difficult to tolerate; 104 patients (65%) required a dose reduction or dose delay during treatment due to toxicity. CONCLUSION: The TCHP regimen, which combines chemotherapy and HER2-directed therapy is effective at obtaining pCR in patients with locally advanced HER2+ breast cancer. These results suggest that the dose intensity of the individual agents did not have a significant impact on pCR rates. Given these findings, providers may be more comfortable allowing dose reductions for greater patient tolerability without sacrificing efficacy.
BACKGROUND: Neoadjuvant chemotherapy is the cornerstone treatment for locally advanced breast cancer. Balancing toxicity and efficacy are a common concern of patients treated with chemotherapy. OBJECTIVE: The objective of this study was to determine the impact of dose intensity on pathologic complete response (pCR) at the time of surgery in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. PATIENTS AND METHODS: A retrospective, single-center review was conducted on patients with HER2+ breast cancer who received neoadjuvant docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP) followed by definitive surgery. RESULTS: A total of 159 patients were included in the analysis; pCR was obtained in 66 patients (42%). There was no statistically significant difference between the mean dose intensity of each of the individual agents in TCHP and pCR rates. The mean overall dose intensity of docetaxel, carboplatin, trastuzumab and pertuzumab was 90.5%, 90.9%, 97.5%, and 93.9%, respectively. Although higher chemotherapy dose intensity (> 85%) was associated with higher pCR rates, no statistically significant difference was found compared with chemotherapy dose intensity < 85%. The TCHP regimen was difficult to tolerate; 104 patients (65%) required a dose reduction or dose delay during treatment due to toxicity. CONCLUSION: The TCHP regimen, which combines chemotherapy and HER2-directed therapy is effective at obtaining pCR in patients with locally advanced HER2+ breast cancer. These results suggest that the dose intensity of the individual agents did not have a significant impact on pCR rates. Given these findings, providers may be more comfortable allowing dose reductions for greater patient tolerability without sacrificing efficacy.
Authors: Mette S van Ramshorst; Anna van der Voort; Erik D van Werkhoven; Ingrid A Mandjes; Inge Kemper; Vincent O Dezentjé; Irma M Oving; Aafke H Honkoop; Lidwine W Tick; Agnes J van de Wouw; Caroline M Mandigers; Laurence J van Warmerdam; Jelle Wesseling; Marie-Jeanne T Vrancken Peeters; Sabine C Linn; Gabe S Sonke Journal: Lancet Oncol Date: 2018-11-06 Impact factor: 41.316
Authors: W Fraser Symmans; Caimiao Wei; Rebekah Gould; Xian Yu; Ya Zhang; Mei Liu; Andrew Walls; Alex Bousamra; Maheshwari Ramineni; Bruno Sinn; Kelly Hunt; Thomas A Buchholz; Vicente Valero; Aman U Buzdar; Wei Yang; Abenaa M Brewster; Stacy Moulder; Lajos Pusztai; Christos Hatzis; Gabriel N Hortobagyi Journal: J Clin Oncol Date: 2017-01-30 Impact factor: 44.544
Authors: Andreas Schneeweiss; Stephen Chia; Tamas Hickish; Vernon Harvey; Alexandru Eniu; Maeve Waldron-Lynch; Jennifer Eng-Wong; Sarah Kirk; Javier Cortés Journal: Eur J Cancer Date: 2017-12-08 Impact factor: 9.162
Authors: Luca Gianni; Tadeusz Pienkowski; Young-Hyuck Im; Ling-Ming Tseng; Mei-Ching Liu; Ana Lluch; Elżbieta Starosławska; Juan de la Haba-Rodriguez; Seock-Ah Im; Jose Luiz Pedrini; Brigitte Poirier; Paolo Morandi; Vladimir Semiglazov; Vichien Srimuninnimit; Giulia Valeria Bianchi; Domenico Magazzù; Virginia McNally; Hannah Douthwaite; Graham Ross; Pinuccia Valagussa Journal: Lancet Oncol Date: 2016-05-11 Impact factor: 41.316
Authors: A Schneeweiss; S Chia; T Hickish; V Harvey; A Eniu; R Hegg; C Tausch; J H Seo; Y-F Tsai; J Ratnayake; V McNally; G Ross; J Cortés Journal: Ann Oncol Date: 2013-05-22 Impact factor: 32.976