Mini Oral Session on head and neck cancer

For his discussion of the mini-oral session on head and neck cancer at ESMO 2024, Dr Michael Saerens, medical oncologist at the University Hospital Ghent selected five interesting presentations.

The first two of these presentations focussed on the use of cisplatin at a weekly dose of 40 mg/m2. JCOG1008 is a randomized phase II/III trial comparing cisplatin at a weekly dose of 40 mg/m2 to a three-weekly dose of 100 mg/m2 both in combination with radiotherapy (RT, 66 Gy over 33 fractions) in post-operative high-risk squamous cell carcinoma of the head and neck (SCCHN).1 The final analysis of this trial (median follow-up: 5.6 years) confirmed non-inferiority for the weekly 40 mg/m2 dose, with a 5-year overall survival (OS) rate of 71.2% as compared to 58.7% with the three-weekly 100 mg/m2 dose (HR[95%CI]: 0.76[0.52-1.12]).1 Furthermore, final results of the RADIO trial showed that a weekly dose of 40 mg/m2 cisplatin came with a significantly lower incidence of grade ≥2 ototoxicity than the 3-weekly 100 mg/m2 dose.2 In this trial, grade ≥2 hearing impairment at 1 year was observed in 64.0% of patients treated with the 3-weekly dose as compared to 40.8% with the weekly regimen (HR[95%CI]: 0.39[0.17-0.87]; p=0.027).2 

The mini-oral session also featured the final results of the randomized phase III GORTEC 2017-01 REACH trial. In this study, the combination of avelumab, cetuximab and RT followed by 12 months of avelumab maintenance therapy was compared to standard of care treatment for patients with locally advanced SCCHN (IMRT 70Gy over 6.5 weeks in combination with cisplatin [fit] or cetuximab [unfit]).3 The study did not reveal a significant benefit in PFS, distant recurrence free survival or OS for the avelumab-containing regimen. Furthermore, the addition of avelumab added substantial toxicity to the regimen.3 For Dr Saerens, these negative data fuel the ongoing discussion on the optimal combination of immunotherapy and radiotherapy in the treatment of HNC.

In a randomized, double-blind phase II study, the combination of pembrolizumab with the NOX4 inhibitor setanaxib was compared to pembrolizumab alone in patients with recurrent or metastatic SCCHN. No difference was seen between both treatment arms in terms of the percentage change in tumor size (primary endpoint, -7,88 vs. -12.93). However, the study did show a significant and clinically meaningful improvement in PFS (HR[95%C]: 0.58[0.38-0.89]) and OS (HR[95%C%]: 0.45[0.24-0.85]) vs. 58%) with the addition of setanaxib. Interestingly, the combination with setanaxib also led to a significant increase in CD8+ tumor infiltrating lymphocytes (TILs) in the tumor tissue.4 As such, these data support further investigation of this agent in patients with head and neck cancer (HNC).

A final abstract that was selected by Dr Saerens evaluated whether epigenetic therapy with a low-dose DNA methyltransferase inhibitor (5’azacytidine) could change the microenvironment of anti-PD1 refractory HNC to resensitize these tumors to immunotherapy.5 While the study did show that low-dose 5’azacytidine increased the IFN-ɣ signature in tumors and increased the expression of PD-L1 expression, these changes in the tumor microenvironment did not lead to treatment responses to the combination of 5’azacytidine in combination with fixed doses of durvalumab and tremelimumab.