Danny Rischin1, Madeleine King2, Lizbeth Kenny3, Sandro Porceddu4, Christopher Wratten5, Andrew Macann6, James E Jackson7, Mathias Bressel8, Alan Herschtal8, Richard Fisher8, Tsien Fua9, Charles Lin10, Chen Liu9, Brett G M Hughes11, Margaret McGrath12, Lachlan McDowell13, June Corry14. 1. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia. Electronic address: danny.rischin@petermac.org. 2. University of Sydney, School of Psychology, Sydney Quality of Life Office, Sydney, Australia. 3. Department of Radiation Oncology, Royal Brisbane & Women's Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia. 4. Faculty of Medicine, University of Queensland, Brisbane, Australia; Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Australia. 5. Department of Radiation Oncology, Calvary Mater Hospital and University of Newcastle, Newcastle, Australia. 6. Department of Radiation Oncology, Auckland City Hospital and University of Auckland, Auckland, New Zealand. 7. Icon Cancer Centres, Gold Coast, Australia. 8. Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Australia. 9. Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. 10. Department of Radiation Oncology, Royal Brisbane & Women's Hospital, Brisbane, Australia. 11. Faculty of Medicine, University of Queensland, Brisbane, Australia; Department of Medical Oncology, Royal Brisbane & Women's Hospital, Brisbane, Australia. 12. Department of Medical Oncology, Princess Alexandra Hospital, Brisbane, Australia. 13. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. 14. Genesiscare St Vincent's Hospital, Melbourne, Australia; Department of Medicine, University of Melbourne, Melbourne, Australia.
Abstract
PURPOSE: The excellent prognosis of patients with low-risk human papillomavirus (HPV)- associated oropharyngeal squamous cell carcinoma has led to concerns about overtreatment and excessive toxicity with radiation therapy and cisplatin, leading to interest in de-intensification trials. We investigated whether cetuximab, an epidermal growth factor receptor targeting antibody, when combined with radiation therapy would result in a decrease in symptom burden and toxicity with similar efficacy compared with weekly cisplatin. METHODS AND MATERIALS: TROG12.01, a randomized, multicenter trial involving 15 sites in Australia and New Zealand enrolled patients with HPV-associated oropharyngeal squamous cell carcinoma, American Joint Committee on Cancer 7th edition stage III (excluding T1-2N1) or stage IV (excluding T4 and/or N3 and/or N2b-c if smoking history >10 pack years and/or distant metastases). Patients were randomized (1:1) to receive radiation therapy (70 Gy in 35 fractions) with either weekly cisplatin, 7 doses of 40 mg/m2, or cetuximab, loading dose of 400 mg/m2 followed by 7 weekly doses of 250 mg/m2. The primary outcome was symptom severity assessed by the MD Anderson Symptom Inventory Head and Neck Symptom Severity Scale from baseline to 13 weeks postcompletion of radiation therapy using the area under the curve. Trial was registered on ClinicalTrials.gov: NCT01855451. RESULTS: Between June 17, 2013, and June 7, 2018, 189 patients were enrolled, with 92 in cisplatin arm and 90 in cetuximab included in the main analysis. There was no difference in the primary endpoint of symptom severity; difference in area under the curve cetuximab-cisplatin was 0.05 (95% confidence interval [CI], -0.19, 0.30), P = .66. The T-score (mean number of ≥grade 3 acute adverse events) was 4.35 (standard deviation 2.48) in the cisplatin arm and 3.82 (standard deviation 1.8) in the cetuximab arm, P = .108. The 3-year failure-free survival rates were 93% (95% CI, 86%-97%) in the cisplatin arm and 80% (95% CI, 70%-87%) in the cetuximab arm (hazard ratio = 3.0 [95% CI, 1.2-7.7]); P = .015. CONCLUSIONS: For patients with low-risk HPV-associated oropharyngeal cancer, radiation therapy and cetuximab had inferior failure-free survival without improvement in symptom burden or toxicity compared with radiation therapy and weekly cisplatin. Radiation therapy and cisplatin remain the standard of care.
PURPOSE: The excellent prognosis of patients with low-risk human papillomavirus (HPV)- associated oropharyngeal squamous cell carcinoma has led to concerns about overtreatment and excessive toxicity with radiation therapy and cisplatin, leading to interest in de-intensification trials. We investigated whether cetuximab, an epidermal growth factor receptor targeting antibody, when combined with radiation therapy would result in a decrease in symptom burden and toxicity with similar efficacy compared with weekly cisplatin. METHODS AND MATERIALS: TROG12.01, a randomized, multicenter trial involving 15 sites in Australia and New Zealand enrolled patients with HPV-associated oropharyngeal squamous cell carcinoma, American Joint Committee on Cancer 7th edition stage III (excluding T1-2N1) or stage IV (excluding T4 and/or N3 and/or N2b-c if smoking history >10 pack years and/or distant metastases). Patients were randomized (1:1) to receive radiation therapy (70 Gy in 35 fractions) with either weekly cisplatin, 7 doses of 40 mg/m2, or cetuximab, loading dose of 400 mg/m2 followed by 7 weekly doses of 250 mg/m2. The primary outcome was symptom severity assessed by the MD Anderson Symptom Inventory Head and Neck Symptom Severity Scale from baseline to 13 weeks postcompletion of radiation therapy using the area under the curve. Trial was registered on ClinicalTrials.gov: NCT01855451. RESULTS: Between June 17, 2013, and June 7, 2018, 189 patients were enrolled, with 92 in cisplatin arm and 90 in cetuximab included in the main analysis. There was no difference in the primary endpoint of symptom severity; difference in area under the curve cetuximab-cisplatin was 0.05 (95% confidence interval [CI], -0.19, 0.30), P = .66. The T-score (mean number of ≥grade 3 acute adverse events) was 4.35 (standard deviation 2.48) in the cisplatin arm and 3.82 (standard deviation 1.8) in the cetuximab arm, P = .108. The 3-year failure-free survival rates were 93% (95% CI, 86%-97%) in the cisplatin arm and 80% (95% CI, 70%-87%) in the cetuximab arm (hazard ratio = 3.0 [95% CI, 1.2-7.7]); P = .015. CONCLUSIONS: For patients with low-risk HPV-associated oropharyngeal cancer, radiation therapy and cetuximab had inferior failure-free survival without improvement in symptom burden or toxicity compared with radiation therapy and weekly cisplatin. Radiation therapy and cisplatin remain the standard of care.
Authors: Lova Sun; Danielle Candelieri-Surette; Tori Anglin-Foote; Julie A Lynch; Kara N Maxwell; Christopher D'Avella; Aditi Singh; Erin Aakhus; Roger B Cohen; Robert M Brody Journal: JAMA Otolaryngol Head Neck Surg Date: 2022-09-22 Impact factor: 8.961
Authors: Ari J Rosenberg; Nishant Agrawal; Alexander Pearson; Zhen Gooi; Elizabeth Blair; John Cursio; Aditya Juloori; Daniel Ginat; Adam Howard; Jeffrey Chin; Sara Kochanny; Corey Foster; Nicole Cipriani; Mark Lingen; Evgeny Izumchenko; Tanguy Y Seiwert; Daniel Haraf; Everett E Vokes Journal: Oral Oncol Date: 2021-10-18 Impact factor: 5.972
Authors: James M Price; Hitesh B Mistry; Guy Betts; Eleanor J Cheadle; Lynne Dixon; Kate Garcez; Tim Illidge; Zsuzsanna Iyizoba-Ebozue; Lip Wai Lee; Andrew McPartlin; Robin J D Prestwich; Savvas Papageorgiou; Dylan J Pritchard; Andrew Sykes; Catharine M West; David J Thomson Journal: J Clin Oncol Date: 2022-04-06 Impact factor: 50.717
Authors: B Keam; J-P Machiels; H R Kim; L Licitra; W Golusinski; V Gregoire; Y G Lee; C Belka; Y Guo; S J Rajappa; M Tahara; M Azrif; M K Ang; M-H Yang; C-H Wang; Q S Ng; W I Wan Zamaniah; N Kiyota; S Babu; K Yang; G Curigliano; S Peters; T W Kim; T Yoshino; G Pentheroudakis Journal: ESMO Open Date: 2021-11-26