Proffered paper session in head and neck cancer

Several presentations at ESMO2023 highlighted significant advancements in the field of head and neck cancer research.

In the GORTEC2014-04 “OMET” trial, researchers investigated the escalation and de-escalation treatment strategies for locally advanced (LA) head and neck cancers (HNSCC), aiming to achieve curative outcomes.

This phase 2 study specifically explored the use of stereotactic radiotherapy (SBAR) without concurrent chemotherapy in treating metastasis in HNSCC patients, without compromising survival or quality of life (QoL). Contrary to some previous studies, the results did not show any added benefit of chemotherapy. These findings are particularly relevant for frail patients, suggesting the possibility of postponing intensive treatments, especially in cases with PD-L1 negative lung metastases. Moreover, the study suggested the potential to extend the interval between primary tumour and metastasis treatments.

Interestingly, the research indicated that there was no significant difference in QoL after one year, regardless of the inclusion of chemotherapy, which was unexpected. However, it’s worth noting that the treatment regimen used in this study was somewhat outdated compared to the standard therapy, and there was no comparison with chemotherapy alone. Nevertheless, these data offer valuable insights.

Furthermore, this study serves as a stepping stone toward the presentation of the integration of liquid biopsies, a technique already employed in breast and colorectal cancer treatments. Liquid biopsies could aid in stratifying HNSCC patients with oligometastatic disease. The presented results demonstrated that post-treatment circulating tumour DNA (ctDNA) could predict progression-free survival (PFS) and overall survival (OS) in locally advanced HNSCC patients. The current sensitivity of the test stands at 78%, so further improvements are necessary. Notably, the selected genes for analysis were derived from tumour biology rather than a standard commercial test, showcasing a novel approach. Exploring additional techniques such as methylation and copy number variations could further enhance the accuracy of these findings.

Combining the insights from this study, which underscored the limited efficacy of chemotherapy, with the potential of ctDNA biomarkers, offers the prospect of tailoring a more precise therapy regimen for the patient population. These biomarkers also hold promise for patient follow-up, although questions regarding the timing of blood sample collection and the necessity of CT follow-ups for ctDNA-negative cases remain.

In the MACH-EGFR meta-analysis, the combined use of anti-EGFR treatment with chemotherapy or its substitution by anti-EGFR therapy was explored. The analysis of extensive data confirmed that add-on therapy was not advantageous. EGFR inhibitors demonstrated benefits primarily in patients under 50 years old, a demographic distinct from the general population with a history of long-term nicotine exposure. Notably, patients with P16 negative mutations, associated with poor prognosis, might benefit from anti-EGFR therapy. However, replacing chemotherapy with anti-EGFR treatment yielded negative results. Chemotherapy was reaffirmed as the cornerstone of treatment for locally advanced HNSCC patients, particularly for female patients, those with oropharyngeal cancer, and nonsmokers, especially in the induction setting.

On a disappointing note, the results of the INTERLINK-1 study revealed limited progress. Following immune checkpoint inhibition and platinum-based chemotherapy, patients were administered cetuximab alone or in combination with monalizumab, a novel anti-NKG2A drug. This combination did not demonstrate additional benefits in terms of overall survival (OS), progression-free survival (PFS), or overall response rate (ORR) compared to cetuximab alone. Consequently, there are currently limited second-line treatment options available for these patients.

Reference:

Thariat J. – OMITting frontline chemotherapy in head and neck cancer (HNSCC) patients with 1-3 oligometastases using stereotactic ablative radiotherapy (SABR), the GORTEC 2014-04 “OMET” randomized phase 2 trial. ESMO 2023 – #853O

Honoré N. – Minimal residual disease (MRD) diagnosed by a plasma tumor-agnostic circulating tumor DNA (ctDNA) assay after curative therapy in locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) predicts disease relapse and survival. ESMO2023 – #858O

Blanchard P. – MACH-EGFR: Individual patient data (IPD) meta-analysis of anti-EGFR monoclonal antibodies (Ab) in patients (pts) with locally advanced (LA) squamous cell carcinomas of head and neck (SCCHN). ESMO2023 -#857O

Fayette J. – INTERLINK-1: Phase 3 study of cetuximab (CTX) ± monalizumab (M) in participants (pts) with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) with disease progression on/after platinum chemotherapy (CT) and previously treated with an immune checkpoint inhibitor (ICI). ESMO2023 – #854O