Squamous cell carcinomas of the head and neck (SCCHN) are a complex group of cancers that present in a very heterogeneous fashion. To complicate things further, patients often do not seek treatment until their cancer is at an advanced stage and has spread (metastasis). The EORTC UPSTREAM trial set out to investigate the effect of targeting treatment to the specific gene alteration (biomarker) found in an individual patient’s tumour. Patients for whom no pre-specified biomarkers are identified in their tumour are treated by immunotherapy. Results from one group in the trial treated with immunotherapy were published recently in the European Journal of Cancer*.
Between November 2017 and August 2018, the Phase 2 trial enrolled 72 patients with SCCHN recurrent metastases whose disease had progressed after being given platinum-based chemotherapy. Of these, 26 who had no specific biomarkers to target, or where the tumour biopsy was not of sufficient quality to determine them, received treatment with monalizumab, a monoclonal antibody that prevents cancer cells blocking immune response to the tumour.
Patients in this group showed little response to the experimental treatment. As a result, there was no further recruitment to the monalizumab alone group, and this part of the trial was closed. Disease control was seen in six patients with stable disease, and minor responses to treatment in 20 with progressive disease. The median duration of stable disease was 3.8 months. Median progression-free survival (the length of time that a patient lives with the disease, but it does not get worse) was 1.7 months, and overall survival 6.7 months.
The researchers will continue the trial in the other groups. Despite the disappointing results among the single therapy patients, they believe that their results demonstrate the feasibility of the UPSTREAM trial.
“Umbrella trials such as UPSTREAM look at how well drugs and treatments work in patients with the same type of cancer but different biomarkers. Even though we have seen that monotherapy with monalizumab has a negligible effect on recurrent SCCHN, we are hopeful that, in those patients where we have been able to identity biomarkers, a combination of treatments will have a better effect. UPSTREAM is currently investigating monalizumab in combination with durvalumab, and a randomised Phase 3 study will compare cetuximab, another antibody that targets damage to the epidermal growth factor receptor, with or without monalizumab” says Principal Investigator Dr Rachel Galot, from the Cliniques Universitaires Saint-Luc, Brussels, Belgium. “We expect to have further results from the trial in the next six months”.
*Galot R, Saada-Bouzid E, Daste A, Even C, Debruyne P, Henry S, Zanetta S, Rutten A, Licitra L, Canon JL, Kaminsky MC, Specenier P, Rottey S, Dirix L, Raveloarivahy T, Fortpied C, Vanlancker M, Govaerts AS, Machiels JP. A phase II study of monalizumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck: results of the I1 cohort of the EORTC-HNCG-1559 trial (UPSTREAM). Eur J Cancer 2021. https://doi.org/10.1016/j.ejca.2021.09.003