L Amiri-Kordestani1, D Xie2, S M Tolaney3, E Bloomquist2, S Tang2, A Ibrahim4, K B Goldberg5, M R Theoret6, R Pazdur6, R Sridhara5, E P Winer3, J A Beaver4. 1. Office of Oncologic Diseases, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring. Electronic address: Laleh.AmiriKordestani@fda.hhs.gov. 2. Office of Biostatistics, Division of Biometrics V, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, USA. 3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA. 4. Office of Oncologic Diseases, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring. 5. Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, USA. 6. Office of Oncologic Diseases, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring; Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, USA.
Abstract
BACKGROUND: Although the Adjuvant Paclitaxel and Trastuzumab (APT) trial has been adopted clinically, single-arm trials have limitations, and interest remains whether these patients with small node-negative human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC) would benefit from more intensive chemotherapy. This analysis explored whether external controls can contextualize single-arm studies to add to clinical decision making in the use of de-escalated therapy in patients with low-risk HER2-positive EBC. PATIENTS AND METHODS: Patient-level data from five randomized trials supporting drug approval in adjuvant HER2-positive EBC were pooled, and patients with low-risk EBC were selected (n = 1770). Patients treated concurrently with trastuzumab and either anthracycline/cyclophosphamide/taxane/trastuzumab (ACTH) or taxane/carboplatin/trastuzumab (TCH; n = 1366) were matched (1:1) to patients treated with paclitaxel and trastuzumab (TH) in the APT trial (n = 406) using propensity scores. Patients treated with anthracycline/cyclophosphamide/taxane (ACT; n = 374) were also matched (1:1) to those treated with TH. Propensity scores were estimated using covariates of age, tumor stage, estrogen receptor status, progesterone receptor status, and histological grade. RESULTS: After matching, the estimated probabilities of invasive disease-free survival (iDFS) at 3 and 5 years were 98.6% and 96.5% in the TH arm, and 96.6% and 92.9% in the ACTH/TCH arm, respectively. The estimated probabilities of overall survival (OS) at 3 and 5 years were 99.7% and 99.3% in the TH arm, and 99.0% and 97.4% in the ACTH/TCH arm, respectively. Comparing the TH arm with the ACT arm in the matched sample, the estimated difference in iDFS was 7.5% (TH 98.8% and ACT 91.3%) at 3 years and 12.6% (TH 96.1% and ACT 83.5%) at 5 years. The estimated difference in OS was 2.6% (TH 100% and ACT 97.4%) at 3 years, and 5.3% (TH 99.3% and ACT 94.0%) at 5 years. CONCLUSIONS: Our analyses suggest that patients' outcomes in both arms were in general similar, thus providing additional reassurance regarding de-escalation of therapy. Published by Elsevier Ltd.
BACKGROUND: Although the Adjuvant Paclitaxel and Trastuzumab (APT) trial has been adopted clinically, single-arm trials have limitations, and interest remains whether these patients with small node-negative human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC) would benefit from more intensive chemotherapy. This analysis explored whether external controls can contextualize single-arm studies to add to clinical decision making in the use of de-escalated therapy in patients with low-risk HER2-positive EBC. PATIENTS AND METHODS: Patient-level data from five randomized trials supporting drug approval in adjuvant HER2-positive EBC were pooled, and patients with low-risk EBC were selected (n = 1770). Patients treated concurrently with trastuzumab and either anthracycline/cyclophosphamide/taxane/trastuzumab (ACTH) or taxane/carboplatin/trastuzumab (TCH; n = 1366) were matched (1:1) to patients treated with paclitaxel and trastuzumab (TH) in the APT trial (n = 406) using propensity scores. Patients treated with anthracycline/cyclophosphamide/taxane (ACT; n = 374) were also matched (1:1) to those treated with TH. Propensity scores were estimated using covariates of age, tumor stage, estrogen receptor status, progesterone receptor status, and histological grade. RESULTS: After matching, the estimated probabilities of invasive disease-free survival (iDFS) at 3 and 5 years were 98.6% and 96.5% in the TH arm, and 96.6% and 92.9% in the ACTH/TCH arm, respectively. The estimated probabilities of overall survival (OS) at 3 and 5 years were 99.7% and 99.3% in the TH arm, and 99.0% and 97.4% in the ACTH/TCH arm, respectively. Comparing the TH arm with the ACT arm in the matched sample, the estimated difference in iDFS was 7.5% (TH 98.8% and ACT 91.3%) at 3 years and 12.6% (TH 96.1% and ACT 83.5%) at 5 years. The estimated difference in OS was 2.6% (TH 100% and ACT 97.4%) at 3 years, and 5.3% (TH 99.3% and ACT 94.0%) at 5 years. CONCLUSIONS: Our analyses suggest that patients' outcomes in both arms were in general similar, thus providing additional reassurance regarding de-escalation of therapy. Published by Elsevier Ltd.
Authors: Rifaquat Rahman; Steffen Ventz; Jon McDunn; Bill Louv; Irmarie Reyes-Rivera; Mei-Yin C Polley; Fahar Merchant; Lauren E Abrey; Joshua E Allen; Laura K Aguilar; Estuardo Aguilar-Cordova; David Arons; Kirk Tanner; Stephen Bagley; Mustafa Khasraw; Timothy Cloughesy; Patrick Y Wen; Brian M Alexander; Lorenzo Trippa Journal: Lancet Oncol Date: 2021-10 Impact factor: 41.316
Authors: Julie A Schneider; Yutao Gong; Kirsten B Goldberg; Paul G Kluetz; Marc R Theoret; Laleh Amiri-Kordestani; Julia A Beaver; Lola Fashoyin-Aje; Nicole J Gormley; Adnan A Jaigirdar; Steven J Lemery; Pallavi S Mishra-Kalyani; Gregory H Reaman; Donna R Rivera; Wendy S Rubinstein; Harpreet Singh; Rajeshwari Sridhara; Richard Pazdur Journal: Clin Cancer Res Date: 2021-10-01 Impact factor: 12.531