Outcome of Targeted Therapy Recommendations for Metastatic and Recurrent Head and Neck Cancers

Abstract

Recurrent/metastatic (R/M) head and neck cancers bear a poor prognosis. In this analysis, we examined the efficacy and the outcome of targeted therapy recommendations based on the patients’ molecular tumor portrait after failure of all standard therapy options. In this single-center, real-world retrospective analysis of our platform for precision medicine, we analyzed the molecular profile of 50 patients diagnosed with R/M head and neck cancer. Tumor samples of the patients were examined using next-generation sequencing panels of mutation hotspots, microsatellite instability (MSI) testing, and immunohistochemistry (IHC). In 31 cases (62.0% of all patients), a molecular-driven targeted therapy approach was recommended. Eventually, 14 patients (28%) received the suggested targeted therapy. Six of fourteen patients (43%) achieved stable disease conditions and four patients (29%) experienced a progressive disease. The median time to treatment failure was 2.8 months. Therapy recommendations were significantly more often issued for men (p = 0.037) than for women. This analysis demonstrated that precision medicine provided the basis for molecular-driven therapy recommendations in over half of the patients with advanced therapy refractory head and neck cancers, with significantly more therapy recommendations for men. Our analysis showed that although precision medicine approaches are implementable and feasible for the management of recurrent/metastatic head and neck cancers in daily clinical routine, there are major limitations and challenges that have to be overcome.

Therapeutic Targeting of FGFR Signaling in Head and Neck Cancer

“…76 In addition, another HNC patient with FGF3 and FGF19 amplifications achieved stable disease for 4 months after ponatinib treatment, a multi-target FGFR inhibitor. 77 In 2 phase I clinical trials of rogaratinib, out of 10 HNSCC patients who received rogaratinib, 2 patients achieved partial response and 4 patients showed stable disease, 51,52 indicating the efficacy of FGFR inhibitors in HNSCC patients. Furthermore, 1 out of 9 HNC patients achieved partial response in a phase I clinical trial of pemigatinib.…”

“…In fact, one HNSCC patient with gene amplifications of multiple FGFs, including FGF3, FGF4, FGF6, FGF19, and FGF23, achieved a complete response to an FGFR inhibitor 76 . In addition, another HNC patient with FGF3 and FGF19 amplifications achieved stable disease for 4 months after ponatinib treatment, a multi-target FGFR inhibitor 77 . In 2 phase I clinical trials of rogaratinib, out of 10 HNSCC patients who received rogaratinib, 2 patients achieved partial response and 4 patients showed stable disease, 51,52 indicating the efficacy of FGFR inhibitors in HNSCC patients.…”

Application of mTORC1 Inhibitors for Tissue-Agnostic Management of Standard-Therapy-Refractory Solid Tumors

“…To assess the immunostaining intensity for the antigens EGFR, mTOR, PDGFRA, PDGFRB, and PTEN, a combinative semi-quantitative score was used. For a comprehensive description of the IHC, we refer to our previous work [9].…”