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

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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. / 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.

In: Journal of Clinical Oncology , Vol. 33, No. 35, 10.12.2015, p. 4202-4209.

Research output: Contribution to journalArticlepeer-review

Harvard

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 , vol. 33, no. 35, pp. 4202-4209. https://doi.org/10.1200/JCO.2015.61.4370

APA

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., ... 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), 4202-4209. https://doi.org/10.1200/JCO.2015.61.4370

Vancouver

Author

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. / 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. In: Journal of Clinical Oncology . 2015 ; Vol. 33, No. 35. pp. 4202-4209.

Bibtex

@article{c7cc5542b0b146ae9c2581efd077be1c,
title = "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",
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.",
author = "Kevin Harrington and Stephane Temam and Hisham Mehanna and Anil D'Cruz and Minish Jain and Ida D'Onofrio and Georgy Manikhas and Zsuzsanna Horvath and Yan Sun and Stefan Dietzsch and Pavol Dubinsky and Petra Holeckova and Iman El-Hariry and Natalie Franklin and Nigel Biswas-Baldwin and Philippe Legenne and Paul Wissel and Thelma Netherway and John Farrell and Catherine Ellis and Jing Wang-Silvanto and Mayur Amonkar and Nazma Ahmed and Sergio Santillana and Jean Bourhis",
note = "{\textcopyright} 2015 by American Society of Clinical Oncology.",
year = "2015",
month = dec,
day = "10",
doi = "10.1200/JCO.2015.61.4370",
language = "English",
volume = "33",
pages = "4202--4209",
journal = "Journal of Clinical Oncology ",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "35",

}

RIS

TY - JOUR

T1 - 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

T2 - a phase III, randomized, double-blind, placebo-controlled study

AU - Harrington, Kevin

AU - Temam, Stephane

AU - Mehanna, Hisham

AU - D'Cruz, Anil

AU - Jain, Minish

AU - D'Onofrio, Ida

AU - Manikhas, Georgy

AU - Horvath, Zsuzsanna

AU - Sun, Yan

AU - Dietzsch, Stefan

AU - Dubinsky, Pavol

AU - Holeckova, Petra

AU - El-Hariry, Iman

AU - Franklin, Natalie

AU - Biswas-Baldwin, Nigel

AU - Legenne, Philippe

AU - Wissel, Paul

AU - Netherway, Thelma

AU - Farrell, John

AU - Ellis, Catherine

AU - Wang-Silvanto, Jing

AU - Amonkar, Mayur

AU - Ahmed, Nazma

AU - Santillana, Sergio

AU - Bourhis, Jean

N1 - © 2015 by American Society of Clinical Oncology.

PY - 2015/12/10

Y1 - 2015/12/10

N2 - 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.

AB - 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.

U2 - 10.1200/JCO.2015.61.4370

DO - 10.1200/JCO.2015.61.4370

M3 - Article

C2 - 26527790

VL - 33

SP - 4202

EP - 4209

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 35

ER -