Personalized biomarker-based treatment strategy for patients with squamous cell carcinoma of the head and neck: EORTC position and approach

Abstract

The molecular landscape of squamous cell carcinoma of the head and the neck (SCCHN) has been characterized and actionable or targetable genomic alterations have been identified. However, targeted therapies have very limited activity in unselected SCCHN, and the current treatment strategy is still based on tumor location and disease stage and not on tumor biology. Trying to select upfront the patients who will benefit from a specific treatment might be a way to improve patients' outcome. With the objective of optimizing the activity of targeted therapies and immunotherapy, we have designed an umbrella biomarker-driven study dedicated to recurrent and/or metastatic SCCHN patients (EORTC-1559-HNCG, NCT03088059). In this article, we review not only the different trial designs for biomarker-driven studies with their respective advantages and opportunities but also the potential pitfalls that led to the design of the EORTC-1559-HNCG protocol. We also discuss the scientific and logistic challenges of biomarker-driven trials.

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

“…Some biomarkers have shown predictive value for outcomes with standard anticancer therapies, including platinum agents, cetuximab‐based chemotherapy, panitumumab‐based chemotherapy, afatinib, radiotherapy, concurrent chemoradiotherapy (CCRT), and immunotherapy . Such biomarkers are particularly important for clinical trial design, as they can aid in patient selection or stratification at randomization, serve as treatment‐monitoring tools, and help predict which specific patient groups are likely to derive the greatest benefit from a particular treatment.…”

“…Patients positive for p16 have shown a greater response to, and improved overall outcomes with radiotherapy, as well as improved outcomes from CTC count during treatment (CCRT), vs those with p16 nonexpression. In addition, some studies indicate a predictive role for p16 status in patients receiving EGFR‐targeted therapy for HNSCC, including cetuximab plus chemotherapy, panitumumab plus chemotherapy (vs chemotherapy alone), and afatinib …”

“…For example, as briefly described above, p16 status appears to influence response to EGFR‐targeted therapies. Patients with p16‐positive tumors responded well to cetuximab‐based therapy, those with p16‐negative tumors responded better to panitumumab‐based therapy and afatinib . In the phase III LUX‐Head&Neck 1 (LUX‐H&N1) trial, 2nd line afatinib significantly improved PFS vs methotrexate in patients with recurrent/metastatic HNSCC.…”

“…In addition, some studies indicate a predictive role for p16 status in patients receiving EGFR-targeted therapy for HNSCC, including cetuximab plus chemotherapy, 46 panitumumab plus chemotherapy (vs chemotherapy alone 57 ), and afatinib. 58,59 As excellent outcomes, in general, can be achieved in HPV-positive HNSCC, the reasonable next step is to deintensify therapy, especially radiotherapy, to minimize treatment-related toxicities and improve quality of life without compromising survival. 110,111 One thing to be noticed is that the de-intensification needs to happen carefully and only within the confines of a clinical trial.…”

“…Patients with p16-positive tumors responded well to cetuximabbased therapy, 41,46 those with p16-negative tumors responded better to panitumumab-based therapy 57,74 and afatinib. 58,59 In the phase III LUX-Head&Neck 1 (LUX-H&N1) trial, 2nd line afatinib significantly improved PFS vs methotrexate in patients with recurrent/metastatic HNSCC. In subgroup analysis, patients who have benefited from afatinib were identified in those with p16 neg , EGFR amplified , HER3 low , PTEN high status.…”