Martin D Forster1, Magnus T Dillon2, Judit Kocsis3, Éva Remenár4, Gabor Pajkos5, Frederic Rolland6, Jonathan Greenberg7, Kevin J Harrington8. 1. Department of Oncology, UCL Cancer Institute/University College London Hospitals, London, UK. 2. Head and Neck Unit, Royal Marsden Hospital/Institute of Cancer Research, National Institute of Health Research Biomedical Research Center, London, UK. 3. Oncology Department, Debrecen University Clinical Center, Debrecen, Hungary; Department of Oncoradiology, Bács-kiskun County Teaching Hospital (BKMK) Centre of Oncoradiology, Kecskemét, Hungary. 4. Hospitalier Order of Saint John of God Hospital Buda, Budapest, Hungary. 5. Department of Oncoradiology, Bács-kiskun County Teaching Hospital (BKMK) Centre of Oncoradiology, Kecskemét, Hungary. 6. Department of Medical Oncology, Institut de Cancerologie de l'Ouest (ICO) - Site René Gauducheau, Saint-Herblain, France. 7. Research and Development Oncology, Daiichi Sankyo, Edison, NJ, USA. 8. Head and Neck Unit, Royal Marsden Hospital/Institute of Cancer Research, National Institute of Health Research Biomedical Research Center, London, UK. Electronic address: Kevin.Harrington@icr.ac.uk.
Abstract
BACKGROUND: The fully human monoclonal antibody patritumab blocks HER3 activation, a resistance mechanism to cetuximab, induced by heregulin (HRG). A phase Ib study in recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) demonstrated tolerability and tumour response of patritumab + cetuximab + platinum. METHODS: This was a randomised, double-blind, phase II study of patritumab + cetuximab with platinum-based therapy for first-line treatment of R/M SCCHN (Clinicaltrials.gov identifier: NCT02633800). Patients aged ≥18 years receivedpatritumab or placebo, both combined with cetuximab + cisplatin or carboplatin. Co-primary end-points were progression-free survival (PFS) in the intent-to-treat (ITT) and the high-expression HRG (HRG high) populations. RESULTS:Eighty-seven patients (n = 43 in the patritumab group; n = 44 in placebo group) enrolled. A median (range) of 6.5 (1-24) patritumab cycles were completed. Median PFS was similar between the patritumab group and placebo group in the ITT population (5.6 versus 5.5 months; hazard ratio [HR] 0.99 [95% confidence interval [CI], 0.6-1.7]; P = 0.96) and HRG-high subgroup (n = 51; 5.6 versus 5.6 months; HR 0.93 [95% CI, 0.5-1.8]; P = 0.82). Median overall survival in the ITT population was also similar (10.0 versus 12.7 months; HR 1.3 [95% CI, 0.69-2.29]; P = 0.46). All patients experienced ≥1 treatment-emergent adverse event (TEAE). Grade ≥III TEAEs were more frequent in the patritumab than the placebo group (84.1% versus 60.5%). The most common grade ≥III patritumab-related TEAE in the patritumab group (20.5% overall) was rash (6.8%). CONCLUSION:Patritumab + cetuximab + platinum was tolerable but not superior to cetuximab + platinum.
RCT Entities:
BACKGROUND: The fully human monoclonal antibody patritumab blocks HER3 activation, a resistance mechanism to cetuximab, induced by heregulin (HRG). A phase Ib study in recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) demonstrated tolerability and tumour response of patritumab + cetuximab + platinum. METHODS: This was a randomised, double-blind, phase II study of patritumab + cetuximab with platinum-based therapy for first-line treatment of R/M SCCHN (Clinicaltrials.gov identifier: NCT02633800). Patients aged ≥18 years received patritumab or placebo, both combined with cetuximab + cisplatin or carboplatin. Co-primary end-points were progression-free survival (PFS) in the intent-to-treat (ITT) and the high-expression HRG (HRG high) populations. RESULTS: Eighty-seven patients (n = 43 in the patritumab group; n = 44 in placebo group) enrolled. A median (range) of 6.5 (1-24) patritumab cycles were completed. Median PFS was similar between the patritumab group and placebo group in the ITT population (5.6 versus 5.5 months; hazard ratio [HR] 0.99 [95% confidence interval [CI], 0.6-1.7]; P = 0.96) and HRG-high subgroup (n = 51; 5.6 versus 5.6 months; HR 0.93 [95% CI, 0.5-1.8]; P = 0.82). Median overall survival in the ITT population was also similar (10.0 versus 12.7 months; HR 1.3 [95% CI, 0.69-2.29]; P = 0.46). All patients experienced ≥1 treatment-emergent adverse event (TEAE). Grade ≥III TEAEs were more frequent in the patritumab than the placebo group (84.1% versus 60.5%). The most common grade ≥III patritumab-related TEAE in the patritumab group (20.5% overall) was rash (6.8%). CONCLUSION:Patritumab + cetuximab + platinum was tolerable but not superior to cetuximab + platinum.
Authors: Mari Iida; Nellie K McDaniel; Kourtney L Kostecki; Noah B Welke; Carlene A Kranjac; Peng Liu; Colin Longhurst; Justine Y Bruce; Seungpyo Hong; Ravi Salgia; Deric L Wheeler Journal: BMC Cancer Date: 2022-04-23 Impact factor: 4.638