Along the line of the ongoing trials, the HNCG is developing projects in 1) post-operative and adjuvant treatment, 2) in locally advanced tumors addressing not only the issue of loco-regional control, but also distant metastases and second primary, 3) in metastatic and recurrent tumors, and 4) in biobanking of tumor and normal tissue specimens.
Immune checkpoint inhibitor in the peri- and post-operative treatment after curative surgery for HNSCC
The current standard of care in post-operative high-risk patients is concomitant chemo-radiotherapy as validated by the EORTC 22931 trial. However, at 5-years, overall survival only reached 53 %, and 18 % of patients will still present a loco-regional recurrence. Furthermore 21% of patients developed distant metastases at 5 years, and a second tumor occurred in 12% of patients at 5 years. Since the publication of this trial, no further progress has been made in the management of these patients with high risk of relapse after surgery.
Immune checkpoint inhibitors including PD-1 and PD-L1 blockade have demonstrated remarkable benefits and a good safety profile/tolerability in the recurrent/metastatic setting in several solid tumors, which may prove effective in the eradication of micro-metastatic disease in the adjuvant setting.
In this framework, the HNCG is elaborating a randomized phase-II study combining immune checkpoint inhibitor(s) delivered concomitantly to chemo-radiotherapy and as adjuvant treatment in high-risk patients after curative surgery.
Emphasis will also be put on the peri-operative period where cancer cells may have been released in the blood stream at the time of surgery. Contacts have been made with different pharmaceutical companies to discuss possible collaborations.
Immune checkpoint inhibitor concomitant to chemo-radiotherapy in locally advanced HNSCC
According to the meta-analysis MACH-NC, the overall survival of patients with locally advanced HNSCC treated with concomitant chemo-radiotherapy only reaches 34% at 5-years. Loco-regional recurrences and distant metastases still occur on average in around 35% and 16% of patients at 5-years, respectively.
In this setting, in collaboration with NCI of Canada (NCIC), the HNCG is elaborating a randomized phase-III protocol for locally advanced HPV-negative HNSCC combining concomitant chemo-radiotherapy with a immune checkpoint blocker administered during and as adjuvant treatment up to one year. For patients with oropharyngeal intermediate risk HPV-positive SCC, discussions are focused around a chemo-sparing randomized phase-II trial.
A pilot study of personalized biomarker-based treatment strategy versus standard therapy in patients with recurrent/metastatic squamous cell carcinoma of the head and neck
Presently, the treatment strategy of patients with HNSCC is based on tumor location and disease stage and not yet on tumor biology. Several molecular pathways in HNSCC are deregulated and abnormal, making this disease potentially attractive for molecular targeted therapy. The aim of our clinical trial is to offer patients tailored targeted therapy based on the results of selected tumor genes sequencing.
Non-curable HNSCC patients will be enrolled in this “umbrella trial”. A fresh tumor biopsy of the recurrence will be performed. Based on the genetic and pathologic results (centralized and performed in a certified laboratory), patients will be assigned to several pre-defined molecular subgroups, e.g. EGFR dependent disease, PI3KCA/mTOR deregulated pathway, FGFR activated pathway, activation of CDK4/6, immunotherapy, and randomized to receive a targeted therapy/immunotherapy or standard therapy (best choice of the investigator).
Biobanking of tumor specimens
In all ongoing HNCG trials, tumor specimens are prospectively collected and stored in appropriate conditions for
future translational research (EORTC 1219 and EORTC 1420), or as part of the main objectives of the clinical trials
(EORTC 90111-24111 and EORTC 1206).
The HNCG also plans to join the EORTC SPECTArare initiative, which intends to prospectively collect tumor samples of rare cancer types (defined as ≤ 6 new cases/100,000/year) to offer patients access to efficient clinical trials. SPECTArare will be based on the EORTC collaborative molecular screening platform model, which has been designed to improve knowledge of the pathobiology of tumors, mutational and gene expression patterns characterizing tumors, and to possibly elaborate specific clinical research projects based on molecularly defined tumor subclassification.
Quality Assurance program for H&N surgery
In Radiation Oncology, quality assurance (QA) programs have been shown to tremendously reduce the variability in patient management across centers and to impact on treatment outcome. Similarly, in line with the SURCARE program of EORTC aiming at establishing general guidelines for QA in surgery, the HNCG is elaborating specific recommendations on performing and reporting surgical procedures in head and neck surgery. Such recommendations should complement existing guidelines on reporting the pathological analysis of surgical specimens.
Long-term Quality of Life and late treatment toxicity
Surviving head and neck cancer is an important objective of cancer treatments. Surviving it with a good or at least acceptable quality of life is even more important. However, little is known about the long-term toxicity of head and neck cancer treatment. In a joint effort with the QLG, we are therefore planning a survey and clinical examination of long-term head and neck cancer survivors.