Harrington, K., Temam, S., Mehanna, H., D'Cruz, A., Jain, M., D'Onofrio, I., Manikhas, G., Horvath, Z., Sun, Y., Dietzsch, S., Dubinsky, P., Holeckova, P., El-Hariry, I., Franklin, N., Biswas-Baldwin, N., Legenne, P., Wissel, P., Netherway, T., Farrell, J., Ellis, C., Wang-Silvanto, J., Amonkar, M., Ahmed, N., Santillana, S., Bourhis, J. (2015) Postoperative Adjuvant Lapatinib and Concurrent Chemoradiotherapy Followed by Maintenance Lapatinib Monotherapy in High-Risk Patients With Resected Squamous Cell Carcinoma of the Head and Neck: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study. JOURNAL OF CLINICAL ONCOLOGY, 33 (35). pp. 4202-4209. ISSN 0732-183X

Full text not available from this repository.

Abstract

Purpose This multicenter phase III study evaluated the efficacy and safety of lapatinib, an epidermal growth factor receptor/ErbB2 inhibitor, administered concomitantly with chemoradiotherapy and as maintenance monotherapy in patients with high-risk surgically treated squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods Patients with resected stage II to IVA SCCHN, with a surgical margin <= 5 mm and/or extracapsular extension, were randomly assigned to chemoradiotherapy (66 Gy total radiation dose and cisplatin 100 mg/m(2) per day administered on days 1, 22, and 43) plus placebo or lapatinib (1,500 mg per day) before and during chemoradiotherapy, followed by 12 months of maintenance monotherapy. Results Six hundred eighty-eight patients were enrolled (lapatinib, n = 346; placebo, n = 342). With a median follow-up time of 35.3 months, the study ended early because of the apparent plateauing of disease-free survival (DFS) events. Median DFS assessed by an independent review committee was 53.6 months and not reached for lapatinib and placebo, respectively (hazard ratio, 1.10; 95% CI, 0.85 to 1.43). Investigator-assessed results confirmed the independent review committee assessment. No significant differences in DFS by human papillomavirus status or overall survival were observed between treatment arms. Similar numbers of patients in both treatment arms experienced adverse events (AEs), with more patients in the lapatinib arm than the placebo arm experiencing serious AEs (48% v 40%, respectively). The most commonly observed treatment-related AEs were diarrhea and rash, both predominantly in the lapatinib arm. Conclusion Addition of lapatinib to chemoradiotherapy and its use as long-term maintenance therapy does not offer any efficacy benefits and had additional toxicity compared with placebo in patients with surgically treated high-risk SCCHN. (C) 2015 by American Society of Clinical Oncology

Item Type:	Article
Authors (ICR Faculty only):	Harrington, Kevin
All Authors:	Harrington, K., Temam, S., Mehanna, H., D'Cruz, A., Jain, M., D'Onofrio, I., Manikhas, G., Horvath, Z., Sun, Y., Dietzsch, S., Dubinsky, P., Holeckova, P., El-Hariry, I., Franklin, N., Biswas-Baldwin, N., Legenne, P., Wissel, P., Netherway, T., Farrell, J., Ellis, C., Wang-Silvanto, J., Amonkar, M., Ahmed, N., Santillana, S., Bourhis, J.
Additional Information:	ISI Document Delivery No.: CX9JG Times Cited: 0 Cited Reference Count: 22 Harrington, Kevin Temam, Stephane Mehanna, Hisham D'Cruz, Anil Jain, Minish D'Onofrio, Ida Manikhas, Georgy Horvath, Zsuzsanna Sun, Yan Dietzsch, Stefan Dubinsky, Pavol Holeckova, Petra El-Hariry, Iman Franklin, Natalie Biswas-Baldwin, Nigel Legenne, Philippe Wissel, Paul Netherway, Thelma Farrell, John Ellis, Catherine Wang-Silvanto, Jing Amonkar, Mayur Ahmed, Nazma Santillana, Sergio Bourhis, Jean GlaxoSmithKline; Novartis Pharmaceuticals Corporation We thank all patients and their families, investigators, and study staff; the independent data monitoring committee; and the BioClinica (independent review committee), EqualEstro (Radiotherapy Quality Assurance), and PAREXEL (independent statistics) teams. The authors also thank Jen Carver, Jhangir Irani, Sejal Patel, Zuheb Ali, and all members of the GlaxoSmithKline central and monitoring team. Lapatinib is an asset of Novartis AG as of March 2, 2015. Editorial support was provided by Karen Yee, PhD, of Fishawack Indicia, funded by GlaxoSmithKline and Novartis Pharmaceuticals Corporation. 0 Amer soc clinical oncology Alexandria 1527-7755
Uncontrolled Keywords:	open-label phase-2 trial chemotherapy radiotherapy multicenter cetuximab therapy cancer combination cisplatin Oncology
Research teams:	ICR divisions > Cancer Biology > Targeted Therapy ICR divisions > Radiotherapy and Imaging > Targeted Therapy Clinical Units > Head & Neck Cancer Unit
Depositing User:	Franziska Noessig
Date Deposited:	04 Jan 2016 12:54
Last Modified:	05 Jan 2016 10:19
URI:	http://publications.icr.ac.uk/id/eprint/14645

Actions (login required)

View Item