Kevin Harrington1, Stephane Temam1, Hisham Mehanna1, Anil D'Cruz1, Minish Jain1, Ida D'Onofrio1, Georgy Manikhas1, Zsuzsanna Horvath1, Yan Sun1, Stefan Dietzsch1, Pavol Dubinsky1, Petra Holeckova1, Iman El-Hariry1, Natalie Franklin1, Nigel Biswas-Baldwin1, Philippe Legenne1, Paul Wissel1, Thelma Netherway1, John Farrell1, Catherine Ellis1, Jing Wang-Silvanto1, Mayur Amonkar1, Nazma Ahmed1, Sergio Santillana1, Jean Bourhis2. 1. 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. 2. 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. jean.bourhis@chuv.ch.
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.
RCT Entities:
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.
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