NEWS

EORTC studies were well-represented at this year’s ASCO conference. Eight abstracts were accepted in total with results from brain, melanoma, thymic carcinoma, prostate cancer and head and neck tumours’ trials presented throughout the event.

Brain tumours

Final results from the CATNON trial¹ were presented by Professor Martin van den Bent. They showed, after following patients for nearly 11 years, that the addition of 12 cycles of the chemotherapy drug temozolomide (TMZ) to brain irradiation in patients with a rare brain cancer called anaplastic glioma, improved overall survival in patients whose cancer had a mutation in the IDH gene (IDHmt). The IDH (isocitrate dehydrogenase) gene plays a role in generating energy within cells and is key to cell health. The mutation (permanent change) makes the cell more fragile. IDHmt patients who received TMZ after irradiation lived around 12 years longer than other patients in the trial.

No benefit was observed when temozolomide chemotherapy was given during brain irradiation and there was also no benefit in patients whose cancer did not show an IDH mutation. The study was carried out by researchers from ten countries worldwide and included 751 adult patients with newly diagnosed anaplastic glioma.

Eternity Study

Glioblastoma is the most common and aggressive type of brain cancer in adults, such that only half of the patients diagnosed with this cancer are alive at 12 months. In addition, fewer than five percent of patients survive for more than five years. These patients are considered to be long-term survivors. The EORTC ETERNITY study is the largest international registry of patients with glioblastoma who survived five years or more. The goal is to describe what makes these tumours different. Professor Michael Weller presented results from a sub-study of ETERNITY², which compared the genetic information of 130 tumours from patients enrolled in the study with those from cohorts with other characteristics. This analysis illustrated the important role of mutations in the MGMT gene. This gene is known to play a key role in fixing DNA in cells when damage occurs.

Melanoma

Results from the primary analysis of data from the EORTC-2139-MG/Columbus-AD trial³ were presented by Professor Alexander van Akkooi. This trial studied the effect of using the targeted anti-cancer drugs encorafenib and binimetinib after surgery in patients with high-risk stage II melanoma with a specific mutation that leads to uncontrolled cell division and growth (a BRAF-V600E/K mutation).

Targeted therapies are cancer treatments that identify and attack cancer cells but leave healthy cells alone. Encorafenib and binimetinib are an approved treatment for melanoma ,that cannot be removed by surgery or that has spread across the body, with a BRAFV600 mutation. The study is the first to investigate this treatment in patients with high-risk stage II melanoma. This is a form of melanoma, which had spread down through the skin and has features that make it more likely to spread.

A total of 110 patients with a BRAF mutation were distributed by chance to either the active treatment (encorafenib+binimetinib) or to placebo. The observed side effects (safety profile) of encorafenib and binimetinib were similar to what has been reported for this combination before. At 12 months of follow-up, researchers found recurrence-free survival (no return of the cancer and remaining alive) was 86% in the encorafenib+binimetinib group and 70% in those on placebo.

Thymus cancers

Thymic carcinoma (TC) and thymoma, malignancies of the thymus (a small gland in the upper chest behind the breastbone), are rare cancers and usually not diagnosed until they are at an advanced stage. The EORTC NIVOTHYM trial⁴ evaluated the use of the immunotherapies nivolumab (N) and ipilimumab (I), in advanced thymoma/carcinoma after exposure to platinum-based therapy-a type of cancer treatment that involves drugs containing platinum, which doctors commonly use to treat various types of slow-growing cancers. The results from the combination treatment group were presented by Dr Nicolas Girard and showed only limited effectiveness in advanced tumours.

Previous results from the trial had shown that nivolumab alone could be a potential option for treatment of TCs, although the results did not achieve statistical significance, and toxicity was a major concern. For the analysis of the combined N and I, 56 patients with thymoma and 48 with TC were enrolled from 15 centres in five countries. However, adding ipilimumab to nivolumab did not give added effectiveness, and the tumour progression-free survival at six months was 21.6%, below the trial’s intended rate of 40%. More patients experienced severe adverse events than in the single agent part of the trial, without any increase in effectiveness.

Prostate cancer

Dr Andrey Soares presented new results from the multi-centre EORTC PEACE III trial⁵, involving a group of 446 men whose metastatic prostate cancer no longer responded to an anti-testosterone treatment (castration-resistant) with bone metastases. The patients were selected using male hormone cancer treatment enzalutamide, alone or in combination with six cycles of Radium 233 (Ra233), a type of internal radiotherapy treatment. It has previously shown that progression-free survival and overall survival were significantly improved in these patients.

The new results show that the addition of Ra233 to enzalutamide improved patients’ prostate-specific antigen (PSA) response time and rates. Increased levels of these enzymes are known to be predictive of bone metastases.

Head and neck tumours

The EORTC IMMUcan project builds our understanding of the tumour microenvironment, i.e. the immune and other cells that surround the tumour. Results of a new analysis⁶, presented by Dr Athénaïs van der Elst, will help understand why some patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) do not respond to anti-PD1 therapies-(specific immunotherapy treatments)

Anti-PD1 therapies are known to improve overall survival in recurrent/metastatic SCCHN, but only a minority of patients achieve durable responses, and factors helping resistance to anti-PD1, remain poorly understood. Now, results from tumour biopsies have shown that specific genomic alterations are associated with resistance to anti-PD1 treatments.

UPSTREAM trial

The EORTC UPSTREAM trial⁷ has investigated the effect of targeted treatment to the specific gene alteration (biomarker) in patients with recurrent or metastatic (R/M) squamous cell carcinomas of the head and neck (SCCHN). The trial set out to investigate individualised treatments for patients with R/M SCCHN whose tumours do not respond to treatment with platinum-based drugs, and who thus had a poor prognosis.

Although some patients do experience a long-lasting response to their treatment, further research is needed to better identify and refine biomarkers in order to explore new treatment strategies.

Treat ctDNA trial

The EORTC 2129-BCG (Treat ctDNA trial)⁸ was presented by Professor Michail Ignatiadis as a Trial in Progress poster. In December 2023, the study started recruiting patients who had been treated for ER+/HER2- breast cancer and were still on hormonal treatment, undergoing monitoring of cancer DNA fragments in blood (ctDNA) every six months. Patients in whom ctDNA is detected are invited to enter the trial, which is investigating the use of the hormonal cancer treatment elacestrant in patients who are positive for ctDNA. It aims to find out whether elacestrant can delay the occurrence of metastases or death when compared with standard endocrine therapy.

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