On June 4, 2025 EORTC reported studies were well-represented at this year’s ASCO (Free ASCO Whitepaper) conference, which took place from 30 May to 3 June in Chicago (Press release, EORTC, JUN 4, 2025, View Source [SID1234653707]). Eight abstracts were accepted, three for oral presentation and five as posters.
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"This is an impressive confirmation of the high quality and clinical importance of our international, patient-centred, academic trials," said EORTC Chief Executive Dr Denis Lacombe.
Brain tumours
Final results from the CATNON trial1 were presented by Professor Martin van den Bent. They showed, after a median follow-up of nearly 11 years, that the addition of 12 cycles of the chemotherapy agent temozolomide (TMZ) to radiotherapy in patients with a particular type of the rare brain tumour anaplastic glioma (an anaplastic astrocytoma) only improved overall survival in the subset of patients with a tumour that had a mutation in the IDH gene (IDHmt). The median overall survival in IDHmt patients who received TMZ after RT was around 12 years.
No benefit was observed when temozolomide chemotherapy was given during radiotherapy and there was also no benefit in patients in which the tumour did not show an IDH mutation. Several biological markers were associated with outcome in patients with an IDH mutated glioma but, importantly, benefit from the treatment was still observed regardless of those markers.
The study was carried out by researchers from ten countries worldwide and randomised 751 adult patients with newly diagnosed anaplastic glioma to radiotherapy alone, radiotherapy with concurrent TMZ, radiotherapy with TMZ given after treatment (adjuvant therapy), and radiotherapy with both concurrent and adjuvant TMZ.
This combined treatment should become the standard of care for patients with anaplastic astrocytoma with an IDH mutation, according to the researchers.
Glioblastoma is the most common and aggressive type of brain tumour in adults, with a poor prognosis and a median survival of approximately 12 months. However, 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 who survived for five years or longer and tries to depict the predictors of long-term survival. Today, the latter are still not clearly established.
Professor Michael Weller presented results from a sub-study of ETERNITY2, which compared the molecular landscape of 130 tumours from patients enrolled in the study with those from different reference cohorts. The sub-analysis illustrates the profound association of alterations in the MGMT gene (a gene encoding a DNA damage repair protein that interferes with the action of alkylating agents) with outcome. However, the results also suggest that there are as yet unidentified clinical and molecular pathways and potential host-dependent features involved in long-term survival. The researchers will be investigating these further in the future.
Melanoma
Results from the primary analysis of data from the EORTC-2139-MG/Columbus-AD trial3 were presented by Professor Alexander van Akkooi. This placebo-controlled randomised trial is studying 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). The drugs target key enzymes in a signaling pathway that occurs in several different cancers.
Targeted therapies are used to treat stage III and IV melanoma and in particular the combination of encorafenib and binimetinib is an approved treatment for unresectable or metastatic melanoma with a BRAFV600 mutation. However, the study is the first to investigate this treatment in patients with high-risk stage II melanoma.
The 110 patients with a BRAF mutation were randomised equally to the active treatment (encorafenib+binimetinib) or to placebo. The safety profile of encorafenib and binimetinib was in line with what had been reported for this combination before. At 12 months follow-up, researchers found recurrence-free survival (no return of the cancer and remaining alive) was 86% in the encorafenib+binimetinib group and 70% among those on placebo. Distant metastasis-free survival at 12 months was 92% for encorafenib+binimetinib and 82% for the placebo arm. A serious treatment-related adverse event occurred in only one patient, and no patients died. Because stage II melanoma has a high risk of recurrence after surgery, these results are particularly encouraging, the researchers say.
Thymus cancers
Thymic carcinoma (TC) and thymoma, malignancies of the thymus, are rare cancers and usually not diagnosed until they are at an advanced stage. The EORTC NIVOTHYM trial4 set out to evaluate the use of the immunotherapies nivolumab (N) and ipilimumab (I), in advanced thymoma/carcinoma after exposure to platinum-based therapy. The results from the combination treatment group were presented by Dr Nicolas Girard and showed only a limited efficacy 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 efficacy, and the progression-free survival at six months was 21.6%, below the trial’s prespecified rate of 40%. More patients experienced severe adverse events than in the single agent part of the trial, without any increase in efficacy. While safety was quite similar, the addition of I to N does not improve patient outcomes, the researchers concluded.
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 randomised equally to the male hormone cancer treatment enzalutamide, alone or in combination with six cycles of Radium 233 (Ra233), a type of internal radiotherapy treatment. The trial was a collaboration between EORTC, CTI CUOG, LACOG, and GETUG/UNICANCER. 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, and alkaline phosphatase (ALP) normalization time and rates after the start of treatment. Elevated levels of these enzymes are known to be predictive of bone metastases.
Head and neck tumours
The EORTC IMMUcan project seeks to enhance 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, immunotherapy treatments that block the activity of proteins involved in programmed cell death.
Anti-PD1 therapies are known to improve overall survival in recurrent/metastatic SCCHN, but only a minority of patients achieve durable responses, and the mechanisms that drive resistance to anti-PD1 remain poorly understood. Now, results from tumour biopsies have shown specific genomic alterations are associated with resistance to anti-PD1 treatments, and also that a high B2M tumour cell expression showed a better overall survival in response to anti-PD1 treatments. The new data provide a rationale to guide the development of therapeutic strategies aimed at reversing acquired resistance to anti-PD1 treatment in SCCHN, and the potential use of B2M expression as a predictive biomarker of response to anti-PD1 therapy.
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.
The latest results from the trial, presented by Professor Jean-Pascal Machiels, showed that, while it was feasible to conduct a biomarker-driven clinical trial in these patients, the clinical activity of the treatments tested is limited. 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.
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 distant metastases or death when compared with standard endocrine therapy.
Secondary trial objectives are to evaluate differences in invasive disease-free survival, relapse-free survival, and overall survival between the elacestrant and standard treatment groups, as well as to uncover any differences in safety and tolerability and patient-reported benefits between them.
"These studies, which have brought together researchers worldwide, provide greater scientific knowledge about existing therapeutic options and offer us new biological hypotheses that can be tested in future trials," said Dr Lacombe.