ESMO 2025: Institut Curie at the forefront of innovation against cancers

Breast cancers

Towards less toxic treatments for women with hormone-dependent breast cancers

Can we adapt the treatments for certain breast cancers and replace chemotherapy with less toxic treatments? This is what the RIBOLARIS clinical trial, promoted by Solti in Spain and coordinated by Unicancer, is evaluating. The preliminary results will be presented in an oral session by Prof. Paul Cottu, medical oncologist at Institut Curie, on October 17, 2025.

Press release coming on October 17

ESME: updated figures for metastatic breast cancers from the largest real-world database in France

From the ESME program (Medical-Economic Epidemio-Strategy, UNICANCER database), the updated data on the overall survival of patients with metastatic breast cancers (HER2+, hormone-dependent and triple negative) will be presented at the ESMO congress. Obtained from more than 33,000 patients, without equivalent in the world in terms of numbers, the up-to-date data show that overall survival is steadily increasing, especially in patients with HER2+ and hormone-dependent breast cancers, probably due to the use of new therapies, such as CDK4/6 inhibitors. The impact of therapeutic innovations has had only a limited effect on the overall survival figures in patients with triple negative breast cancer, highlighting the importance of continuing research for the development of new therapeutic strategies in this cancer.

Neurofibromatosis type 1, aggressiveness factor of breast cancers

Affecting about 1 in 3,000 people, the neurofibromatosis type 1 (NF1) is a hereditary syndrome linked to the NF1 gene (coding for a protein called neurofibromine, which helps regulate cell growth). Patients with this syndrome and with breast cancer showed aggressive characteristics, hypothesizing that NF1 influences the development of tumor disease. In order to answer this question, the work carried out at Institut Curie compared cohorts of breast cancer patients, with or without NF1. The results obtained from about 400 patients reveal that breast cancer in women with NF1 has more aggressive characteristics, associated with a higher risk of contralateral breast cancer, suggesting a consideration of this factor in the monitoring of these women. The data also show that, despite its aggressiveness factors, no impact on overall survival is found, probably thanks to the efficacy of current treatments.

Gynecological cancers

Nearly 18,000 women are affected by gynecological cancers every year in France. These cancers include complex and varied pathologies requiring coordinated and personalized treatment. At the heart of the concerns of Institut Curie and The Women's Cancer Institute (co-founded with PSL University and Inserm), the research and care teams come together to improve diagnosis, strengthen prevention, and guarantee optimal treatment at all phases of the disease adapted to each patient.

Metastatic endometrial cancer: analysis of efficacy and safety data of the combination of immunotherapy and targeted therapy in a French multicenter cohort

Endometrial cancer is the most common gynecological cancer in France, the fourth most common women's cancer, with an estimated 8,000 cases annually¹. The positive results of the Phase 3 Keynote-775 study constituted a turning point in the treatment of advanced endometrial cancers, in which carboplatin chemotherapy has failed thanks to the overall survival benefit conferred by the combination of immunotherapy (pembrolizumab) and targeted therapy (lenvatinib). The application of this therapeutic strategy in a "real-world" population represents a clinical challenge. In order to better understand the effect of this treatment, in particular, its tolerance among older populations and presenting with diseases with different evolutionary profiles, LARENA, a national study co-promoted by Institut Curie and ARCAGY-GINECO, analyzes progression-free survival data, overall survival, and treatment safety. 

The results highlight that in the 351 patients in the cohort, individualization of the initiation dose of lenvatinib allows for less toxicity, without altering efficacy in all patient subgroups.

Ovarian cancers: efficacy of surgery as a standard treatment

Among gynecological cancers, ovarian cancer affects more than 5,000 women in France² every year, most often around the age of 65. In 90% of cases, these are epithelial ovarian cancers, two thirds of which are high-grade serous carcinomas. 

The cytoreductive surgery in the abdominal cavity, which aims to remove tumor tissue, is a central treatment of advanced ovarian cancers. The positioning of such a surgery in Stage IV ovarian cancers nevertheless remains underexplored. Based on the data of the ESME program (Epidemio-Medico-Economic Strategy, UNICANCER base), the teams of Institut Curie have identified the factors influencing the eligibility for surgery in Stage IV serous carcinomas, as well as its impact on overall survival, in more than 6,000 patients. 

The results show that operated patients have significantly better progression-free and overall survival than non-operated patients. Among the operated patients, the criteria that govern a better overall survival are the number of metastatic sites (and therefore the tumor load), the general condition, and the macroscopically complete nature of the surgery. These data confirm the place of surgery in stage IV ovarian cancer.

Institut Curie is a national expert center for the management of uveal melanomas, which are the most common malignant tumors of the eye in adults and for which metastases (often hepatic) are frequent. 

The standard treatment in this case is immunotherapy with tebentafusp, a bispecific antibody (capable of redirecting the patient's CD3+ T lymphocytes against the gp100 glycoprotein expressed by skin cells and melanoma tumor cells). Tebentafusp can be used in about 45% of patients (those with a specific form of HLA (HLA serotype*02:01)³), necessary to trigger this anti-melanoma immunity).

Other immunotherapies have a lower efficacy, illustrating the need to identify new treatment strategies for patients with metastatic uveal melanomas.

A promising new treatment combination

In this context, the Phase 2 PLUME clinical trial aims to evaluate the efficacy and tolerability of the combination of immunotherapy using anti-PD-1 antibodies with targeted treatment. The first results of this study will be presented to you by Dr Manuel Rodrigues, principal investigator of the PLUME clinical trial, and doctor-researcher at Institut Curie in a mini oral session at ESMO on October 18.

Press release coming on October 18
 

Uveal melanoma: genomic profiles to better predict the efficacy of immunotherapy with tebentafusp

A retrospective study conducted at Institut Curie and presented at the ESMO 2025 congress analyzed 168 patients with metastatic uveal melanoma treated with tebentafusp between 2018 and 2024 (patients with a specific form of HLA). The results show an efficacy comparable to that observed in the registration trial of this treatment, which was well tolerated. 

This study reveals that certain genomic profiles (loss of BAP1, monosomy 3, SF3B1/EIF1AX mutations) seem to influence the prognosis and could help to better predict the response to treatment.

Early Together: a French study to evaluate the benefits of supportive care in the management of metastatic uveal melanoma

When uveal melanoma becomes metastatic, symptoms often appear very late and very quickly, making it difficult to implement supportive care. A multicenter phase 3 study, “Early Together,” coordinated by Dr. Sophie Piperno-Neumann, an oncologist at the Institut Curie, evaluates the early introduction of palliative care from the start of oncological treatment in patients with metastatic uveal melanoma, focusing on information needs and supportive care. 

From July 2020 to January 2024, 162 patients were randomized across two participating centers (Paris and Nice): palliative care was introduced according to recommendations for one group. In the other group, palliative care consultations began at the oncologist’s announcement of metastases and continued for one year. 

The results presented at ESMO show no significant difference between the groups; however, further analyses are underway.
 

"Cancers of unknown origin" or "of unknown primary" (CUP) are cancers discovered by the presence of metastases, that is to say when the disease has spread to different tissues, without it being possible to identify the first organ affected. They represent between 2 and 3 % cases of cancers (i.e. approximately 7,000 patients per year in France)⁴ and are especially difficult to care for.

In France, a multidisciplinary consultation meeting (MCM) dedicated to CUP brings together different medical specialties to guide the treatment for each patient. This MCM was created in 2020 and is coordinated at the national level by Institut Curie. 

The analysis of the data of 246 patients who benefited from the expertise of this national MCM between 2020 and 2023 shows that the integration of clinical, pathological, and molecular results is possible in the real world for these diseases with a very poor prognosis. It enabled the identification of the presumed tissue of origin in 70% of cases, making it possible to guide treatment, in particular thanks to therapies targeted at the tissue of origin. The median overall survival of patients who received the guided treatment was 18.6 months, compared to 11 months for patients who received empirical treatment, according to international treatment standards, confirming the benefit of MCM and reference centers for the management of cancers of unknown primary. 

In another CUP study, doctors were interested in brain metastases. Approximately 20% of patients with metastatic cancers have metastases to the brain, of which 15% are cancers of unknown primary. In order to better describe the clinical and epidemiological parameters of these metastases of unknown origin, a retrospective study was conducted on the clinical, pathological, molecular, and survival data of 62 patients (19 French centers), collected as part of the national MCM. Their analysis shows a heterogeneity, especially in tissues of supposed origin, with an overrepresentation of tumors of digestive origin. These data will be supplemented by advanced molecular analyses (genomic, transcriptomic, epigenetic) in order to improve the classification of tumors, which is crucial for treatment adaptation.  

In addition, the results of a retrospective study conducted on 25 patients with cancers of unknown primary (whose data were discussed as part of the national MCM) will also be presented at the congress. It aims to substantiate the data on CUPs with suspicion of an origin in the breast, data remaining limited today. 

These works reveal an over-representation of male patients among the people included in the study, as well as an over-representation of cases of triple negative breast cancers. Thanks to the analyzes carried out by the MCM, these patients were able to receive targeted therapies that had a beneficial effect on overall survival, higher than that usually reported from patients with CUP.
 

Optimizing care with chemotherapy

Work carried out in collaboration with Institut Curie focused on issues related to the administration of platinum salt family chemotherapies, standard treatments in the care of cancer patients. A first study, carried out in collaboration with the Henri Mondor Hospital, focused on the dose of a chemotherapy drug (carboplatin) usually calculated based on an estimate of renal function according to a method that may be distorted in some patients. The research team proposes the use of a new formula that would make it possible to better estimate the renal function of patients, and thus better customize the dose of carboplatin, to avoid over-toxicity.

Moreover, concerning the cisplatin-based chemotherapy, there is no consensus on the hydration protocol to be prescribed in order to avoid renal toxicity of the molecule. The results of an exploratory survey, based on the results of a questionnaire sent to healthcare professionals, reveal that there is heterogeneity in the hydration procedures carried out in France, illustrating the need for national and international recommendations for better patient care.

What is the environmental impact of oncology care?

What do health professionals believe the environmental impact of oncology care is? The analysis of the results of a questionnaire on oncology and ecology shows that most of the oncology health professionals interviewed believe that their specialty has a more harmful effect on the environment than others, in particular in connection with the use of biotherapies, chemotherapy, and radiation therapies, and that this is an element that is not sufficiently taken into account when organizing and designing the care at present.
 

IMMUNOBIL: first results of the study evaluating a combination of immunotherapies in patients with bile duct cancer

Bile duct cancers are rare tumors, affecting around 3,000 to 4,000 people per year in France⁵, very often with a poor prognosis. Until recently, the standard of treatment for first-line bile duct cancer was a combination of chemotherapy, before being replaced by immunotherapy, combined with chemotherapy. 

The IMMUNOBIL Phase 2 clinical trial, promoted by GERCOR, and whose principal investigator is Dr. Cindy Neuzillet, medical oncologist at Institut Curie, aimed to evaluate the efficacy of a combination of immunotherapies using anti-PD-L1 (durvalumab) and anti-CTLA-4 (tremelimumab) antibodies in 212 patients after failure of chemotherapy. The main evaluation criterion on overall survival at 6 months has not been met. "However, the results relating to the analysis of patient survival based on tumor response can be highlighted. We observed that patients whose tumor was stable or shrinking at the first assessment had a very prolonged survival for a second-line treatment population, with 18 months of median overall survival. We have also shown that the PD-L1 CPS score⁶ (combined positive score) of a value greater than five was associated with a longer overall survival, which had not been demonstrated so far in this type of cancer.

This study therefore makes it possible to show that there is a subgroup of patients who benefit more from immunotherapy, and that the PD-L1 CPS score could be one of the markers to identify them, but that it is not sufficient, " specifies Dr Matthieu Delaye, medical oncologist at Institut Curie.

This study is backed by an ancillary program: IMMUNOBIL-SIGN (funded by the Translational Research Program in Cancer, PRT-K) to identify factors involved in the response to immunotherapies in bile duct cancers. "The results of this program could lead to a better understanding of the benefits of immunotherapy, now used on the front line for bile duct cancers, " concludes Dr. Matthieu Delaye.

A new AI tool to better characterize bladder cancers

There are many subtypes of bladder tumor infiltrating the muscle, whose prognosis and response to treatment are variable.

In order to be able to identify them quickly, a study in which the teams of Institut Curie participated, made it possible to develop an AI model, capable of predicting the expression of genes associated with different subtypes of cancer. This tool was designed from histological sections of 297 patients included in the VESPER clinical trial⁷.

The results show that AI is successful in predicting cancer subtypes from samples and could therefore enable the classification of patients in the clinic, without resorting to sequencing.

ENT cancers: five new signatures to follow the evolution of the disease

In patients with advanced or metastatic ENT cancer, the efficacy of immunotherapy (nivolumab) remains limited, with only a 20% response. In order to better follow the evolution of the disease, it is crucial to highlight new biomarkers.

The analysis of the data obtained from 176 patients who participated in various clinical trials allowed the teams of Institut Curie to identify five transcriptomic signatures related to the immune system, associated with progression-free survival of the tumor and overall survival of patients.

In addition, a phase 2 study presented at ESMO, aimed to evaluate the efficacy of a combination of PD-1 immune checkpoint inhibitors with immunotherapy on the evolution of the disease. The negative results thus show that the median progression-free survival was not affected by the additional treatments, even if the response rates are higher.

PEVOsq clinical trial: epigenetic biomarkers identified in patients with squamous cell carcinomas

In squamous cell carcinomas (ENT, anal canal, vulva, penis, cervix, lung), the factors involved in the late course of the disease are little known, which further complicates the monitoring of patients. 

In this context, the PEVOsq clinical trial, piloted by Institut Curie and promoted by UNICANCER, conducted in patients with squamous cell carcinomas, aimed to evaluate the efficacy of an immunotherapy (pembrolizumab) combined with an epimedicine⁷ (vorinostat). Based on the data of 77 patients included in the PEVOsq study, the doctors have highlighted that the state of infiltration of immune cells but also the expression of the HLA gene⁸ play a predictive role in the response to immunotherapy. Moreover, the results of the study reveal the activation of signatures associated with histone-deacetylases – a group of enzymes involved in epigenetic mechanisms – in patients responding positively to immunotherapy, supporting the hypothesis of the role of these enzymes in this response.

Epigenetics to better follow the evolution of tumors

DNA methylation analysis is a promising tool for monitoring cancer progression, and one epigenetic marker is particularly interesting: LINE-1 hypomethylation. Researchers from Institut Curie have evaluated the relevance of the joint analysis of genetic alterations and the LINE-1 methylation status in circulating tumor DNA (ctDNA⁹) of 32 patients with metastatic cancers included in the SHIVA02 trial¹⁰. Their results show that this combined approach strengthens the sensitivity of cancer detection in ctDNA. These two analyses correlate with the response of patients to treatments. 

This study confirms the involvement of LINE-1 hypomethylation as a dynamic monitoring biomarker and highlights the complementarity of genetic and epigenetic alterations to monitor the progression of the disease.

New biomarkers in HER2-mutated lung cancers

About 3% of non-small cell lung cancers are associated with an alteration of the HER2 receptor, known in particular in breast cancers and responsible for the proliferation of tumor cells. The SOHO-01 clinical trial, whose first promising results had been presented at ASCO 2024, aims to evaluate the clinical relevance of the use of a therapy targeting HER2 (sevabertinib). In order to better understand the effects of this treatment, the teams of Institut Curie have managed to identify several biomarkers that would potentially make it possible to follow the evolution of the disease in patients; for example, the presence or absence of a certain HER2 variant or the dynamics of elimination of circulating tumor DNA.