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

Research output: Contribution to journalArticlepeer-review


  • Kevin Harrington
  • Stephane Temam
  • Anil D'Cruz
  • Minish Jain
  • Ida D'Onofrio
  • Georgy Manikhas
  • Zsuzsanna Horvath
  • Yan Sun
  • Stefan Dietzsch
  • Pavol Dubinsky
  • Petra Holeckova
  • Iman El-Hariry
  • Natalie Franklin
  • Nigel Biswas-Baldwin
  • Philippe Legenne
  • Paul Wissel
  • Thelma Netherway
  • John Farrell
  • Catherine Ellis
  • Jing Wang-Silvanto
  • Mayur Amonkar
  • Nazma Ahmed
  • Sergio Santillana
  • Jean Bourhis


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.


Original languageEnglish
Pages (from-to)4202-4209
JournalJournal of Clinical Oncology
Issue number35
Early online date2 Nov 2015
Publication statusPublished - 10 Dec 2015