Kevin Harrington, Institute of Cancer Research and Royal Marsden Hospital, London; Hisham Mehanna, Institute of Head and Neck Studies and Education, University of Birmingham, Birmingham; Natalie Franklin and John Farrell, GlaxoSmithKline, Uxbridge, United Kingdom; Stephane Temam and Jean Bourhis, Institut Gustave- Roussy, Villejuif; Ida D'Onofrio, Hôpital Forcilles, Paris, France; Anil D'Cruz, Tata Memorial Hospital, Mumbai; Minish Jain, Ruby Hall Clinic-Cancer Centre, Pune, India; Georgy Manikhas, St Petersburg City Oncology Dispensary, St Petersburg, Russia; Zsuzsanna Horvath, Szent Imre University Teaching Hospital Budapest, Budapest, Hungary; Yan Sun, Beijing Cancer Hospital, Beijing, China; Stefan Dietzsch, Hospital and Policlinic for Radiation Therapy and Radio-oncology, Leipzig, Germany; Pavol Dubinsky, East Slovakia Cancer Institute, Kosice, Slovakia; Petra Holeckova, Institute of Radiation Oncology, Hospital Na Bulovce, and 1st Medical Faculty of Charles University, Prague, Czech Republic; Iman El-Hariry, Synta Pharmaceutical, Lexington, MA; Paul Wissel and Mayur Amonkar, Novartis Pharmaceuticals, East Hanover, NJ; Catherine Ellis and Sergio Santillana, GlaxoSmithKline, Philadelphia, PA; and Nigel Biswas-Baldwin, Philippe Legenne, Thelma Netherway, Jing Wang-Silvanto, and Nazma Ahmed, Novartis Pharma AG, Basel, Switzerland.
J Clin Oncol. 2015 Dec 10;33(35):4202-9. doi: 10.1200/JCO.2015.61.4370. Epub 2015 Nov 2.
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 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.
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.
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.
这项多中心 III 期研究评估了拉帕替尼（一种表皮生长因子受体/ErbB2 抑制剂）联合放化疗及维持单药治疗高危手术治疗的头颈部鳞状细胞癌（SCCHN）患者的疗效和安全性。
患者为接受手术治疗的 II 至 IVA 期 SCCHN 患者，切缘≤5mm 和/或囊外扩展，随机分配接受放化疗（总剂量 66Gy，顺铂 100mg/m2 ，第 1、22 和 43 天给药）联合安慰剂或拉帕替尼（1500mg/天），在放化疗前和放化疗期间，然后进行 12 个月的维持单药治疗。
共纳入 688 例患者（拉帕替尼组 346 例，安慰剂组 342 例）。中位随访时间为 35.3 个月，由于无疾病进展生存（DFS）事件的明显平台化，研究提前结束。独立审查委员会评估的中位 DFS 分别为拉帕替尼和安慰剂组的 53.6 个月和未达到（风险比，1.10；95%CI，0.85 至 1.43）。研究者评估的结果证实了独立审查委员会的评估。治疗组之间的 DFS 无明显差异与 HPV 状态或总生存相关。两个治疗组发生不良事件（AE）的患者数量相似，拉帕替尼组比安慰剂组发生严重 AE 的患者更多（分别为 48%和 40%）。最常见的治疗相关 AE 是腹泻和皮疹，两者均主要发生在拉帕替尼组。
与安慰剂相比，拉帕替尼联合放化疗及长期维持治疗并未为手术治疗的高危 SCCHN 患者带来任何疗效益处，反而增加了毒性。
