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Randomized Phase II Trial of Ficlatuzumab With or Without Cetuximab in Pan-Refractory, Recurrent/Metastatic Head and Neck Cancer. 2023

Julie E Bauman, and Nabil F Saba, and Denise Roe, and Jessica R Bauman, and John Kaczmar, and Aarti Bhatia, and Jameel Muzaffar, and Ricklie Julian, and Steven Wang, and Shethal Bearelly, and Audrey Baker, and Conor Steuer, and Anshu Giri, and Barbara Burtness, and Sara Centuori, and Carlos Caulin, and Robert Klein, and Kathylynn Saboda, and Stefanie Obara, and Christine H Chung
Division of Hematology/Oncology, Department of Medicine, George Washington (GW) University and GW Cancer Center, Washington, DC.

Primary or acquired resistance to cetuximab, an antiepidermal growth factor receptor monoclonal antibody (mAb), minimizes its utility in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Aberrant hepatocyte growth factor/cMet pathway activation is an established resistance mechanism. Dual pathway targeting may overcome resistance. This multicenter, randomized, noncomparative phase II study evaluated ficlatuzumab, an antihepatocyte growth factor mAb, with or without cetuximab in recurrent/metastatic HNSCC. The primary end point was median progression-free survival (PFS); an arm met significance criteria if the lower bound of the 90% CI excluded the historical control of 2 months. Key eligibility criteria were HNSCC with known human papillomavirus (HPV) status, cetuximab resistance (progression within 6 months of exposure in the definitive or recurrent/metastatic setting), and resistance to platinum and anti-PD-1 mAb. Secondary end points included objective response rate (ORR), toxicity, and the association of HPV status and cMet overexpression with efficacy. Continuous Bayesian futility monitoring was used. From 2018 to 2020, 60 patients were randomly assigned and 58 were treated. Twenty-seven versus 33 patients were allocated to monotherapy versus combination. Arms were balanced for major prognostic factors. The monotherapy arm closed early for futility. The combination arm met prespecified significance criteria with a median PFS of 3.7 months (lower bound 90% CI, 2.3 months; P = .04); the ORR was 6 of 32 (19%), including two complete and four partial responses. Exploratory analyses were limited to the combination arm: the median PFS was 2.3 versus 4.1 months (P = .03) and the ORR was 0 of 16 (0%) versus 6 of 16 (38%; P = .02) in the HPV-positive versus HPV-negative subgroups, respectively. cMet overexpression was associated with reduced hazard of progression in HPV-negative but not HPV-positive disease (P interaction = .02). The ficlatuzumab-cetuximab arm met significance criteria for PFS and warrants phase III development. HPV-negative HNSCC merits consideration as a selection criterion.

UI MeSH Term Description Entries
D009364 Neoplasm Recurrence, Local The local recurrence of a neoplasm following treatment. It arises from microscopic cells of the original neoplasm that have escaped therapeutic intervention and later become clinically visible at the original site. Local Neoplasm Recurrence,Local Neoplasm Recurrences,Locoregional Neoplasm Recurrence,Neoplasm Recurrence, Locoregional,Neoplasm Recurrences, Local,Recurrence, Local Neoplasm,Recurrence, Locoregional Neoplasm,Recurrences, Local Neoplasm,Locoregional Neoplasm Recurrences,Neoplasm Recurrences, Locoregional,Recurrences, Locoregional Neoplasm
D006258 Head and Neck Neoplasms Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651) Cancer of Head and Neck,Head Cancer,Head Neoplasm,Head and Neck Cancer,Head and Neck Neoplasm,Neck Cancer,Neck Neoplasm,Neck Neoplasms,Neoplasms, Upper Aerodigestive Tract,UADT Neoplasm,Upper Aerodigestive Tract Neoplasm,Upper Aerodigestive Tract Neoplasms,Cancer of Head,Cancer of Neck,Cancer of the Head,Cancer of the Head and Neck,Cancer of the Neck,Head Neoplasms,Head, Neck Neoplasms,Neoplasms, Head,Neoplasms, Head and Neck,Neoplasms, Neck,UADT Neoplasms,Cancer, Head,Cancer, Neck,Cancers, Head,Cancers, Neck,Head Cancers,Neck Cancers,Neoplasm, Head,Neoplasm, Neck,Neoplasm, UADT,Neoplasms, UADT
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000068818 Cetuximab A chimeric monoclonal antibody that functions as an ANTINEOPLASTIC AGENT through its binding to the EPIDERMAL GROWTH FACTOR RECEPTOR, where it prevents the binding and signaling action of cell growth and survival factors. C225,Erbitux,IMC C225,IMC-C225,MAb C225
D000077195 Squamous Cell Carcinoma of Head and Neck The most common type of head and neck carcinoma that originates from cells on the surface of the NASAL CAVITY; MOUTH; PARANASAL SINUSES, SALIVARY GLANDS, and LARYNX. Mutations in TNFRSF10B, PTEN, and ING1 genes are associated with this cancer. HNSCC,Head And Neck Squamous Cell Carcinomas,Hypopharyngeal Squamous Cell Carcinoma,Laryngeal Squamous Cell Carcinoma,Oral Cavity Squamous Cell Carcinoma,Oral Squamous Cell Carcinoma,Oral Squamous Cell Carcinomas,Oral Tongue Squamous Cell Carcinoma,Oropharyngeal Squamous Cell Carcinoma,Squamous Cell Carcinoma of Larynx,Squamous Cell Carcinoma of the Larynx,Squamous Cell Carcinoma of the Mouth,Squamous Cell Carcinoma of the Nasal Cavity,Carcinoma, Squamous Cell of Head and Neck,Head and Neck Squamous Cell Carcinoma,Squamous Cell Carcinoma of the Head and Neck,Squamous Cell Carcinoma, Head And Neck
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D000971 Antineoplastic Combined Chemotherapy Protocols The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form. Anticancer Drug Combinations,Antineoplastic Agents, Combined,Antineoplastic Chemotherapy Protocols,Antineoplastic Drug Combinations,Cancer Chemotherapy Protocols,Chemotherapy Protocols, Antineoplastic,Drug Combinations, Antineoplastic,Antineoplastic Combined Chemotherapy Regimens,Combined Antineoplastic Agents,Agent, Combined Antineoplastic,Agents, Combined Antineoplastic,Anticancer Drug Combination,Antineoplastic Agent, Combined,Antineoplastic Chemotherapy Protocol,Antineoplastic Drug Combination,Cancer Chemotherapy Protocol,Chemotherapy Protocol, Antineoplastic,Chemotherapy Protocol, Cancer,Chemotherapy Protocols, Cancer,Combinations, Antineoplastic Drug,Combined Antineoplastic Agent,Drug Combination, Anticancer,Drug Combination, Antineoplastic,Drug Combinations, Anticancer,Protocol, Antineoplastic Chemotherapy,Protocol, Cancer Chemotherapy,Protocols, Antineoplastic Chemotherapy,Protocols, Cancer Chemotherapy
D001499 Bayes Theorem A theorem in probability theory named for Thomas Bayes (1702-1761). In epidemiology, it is used to obtain the probability of disease in a group of people with some characteristic on the basis of the overall rate of that disease and of the likelihood of that characteristic in healthy and diseased individuals. The most familiar application is in clinical decision analysis where it is used for estimating the probability of a particular diagnosis given the appearance of some symptoms or test result. Bayesian Analysis,Bayesian Estimation,Bayesian Forecast,Bayesian Method,Bayesian Prediction,Analysis, Bayesian,Bayesian Approach,Approach, Bayesian,Approachs, Bayesian,Bayesian Approachs,Estimation, Bayesian,Forecast, Bayesian,Method, Bayesian,Prediction, Bayesian,Theorem, Bayes

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