A 96% cure rate: the Cancer Institute of HCL reveals spectacular results of a new treatment for a rare form of pregnancy cancer at ESMO 2024

Stemming from the placenta, trophoblastic gestational diseases affect 1 in 1000 pregnancies in France. If most of them are benign, 10% can become malignant tumours, potentially fatal. After a 4-year study, the National Reference Centre for trophoblastic diseases located in Lyon Sud Hospital (Hospices Civils de Lyon, HCL), has revealed a treatment that eradicates trophoblastic tumours in 25 of the 26 treated patients, which is an extremely rare success rate. This major breakthrough against this form of gestational cancer has been selected to open the Gynaecological cancer session at ESMO 2024 in Barcelona.

?? This is an exceptional result, extremely rare in the history of oncology. This is one of the first time we speak of cancer eradication?. Four years ago, when the study TROPHAMET was launched, the professors Benoit YOU and Pierre-Adrien BOLZE assumed that the association of two types of treatment to fight gestational trophoblastic tumours (GTT) would lead to interesting results. But not to the point of reaching a cure rate of almost 100%, rarely reached in the history of research against cancer.

Occurring after a pregnancy, usually a molar pregnancy but also sometimes after delivery, the GTT is a malignant form of gestational trophoblastic diseases. Considered as a rare cancer, with an estimation of 1 case in 10 000 pregnancies, these gestational trophoblastic tumours, not always properly detected, have a high metastatic potential and are potentially life-threatening without treatment. Traditionally, the treatment consists of intense chemotherapy, distinguishing two GTT categories: “high risk” or “low risk” of chemotherapy resistance. The “low risk” GTD represents 80% of all gestational trophoblastic tumours.

Professors Benoit YOU and Pierre-Adrien BOLZE have focused on the latter category for the TROPHAMET study. Respectively oncologist and gynaecological surgeon, the two doctors are members of the national reference centre of trophoblastic diseases.? Created in 1999 at the Lyon Sud Hospital and led by Pr Fran?ois GOLFIER, this one-of-a-kind centre in France coordinates the follow-up of all patients with gestational trophoblastic diseases in France, including those with GTT, developing after or during a pregnancy and related to a form of “pregnancy cancer”. ?

Combining, for the first time, immunotherapy and chemotherapy

? As a medical oncologist, I provide advice on chemotherapy for these diseases and I am in charge of EPSILyon, the early-phase clinical trials unit of the Cancer Institute of HCL, accredited by the French National Cancer Institute (INCa). In the past, we had the opportunity to evaluate efficacy of innovative therapeutic options and we worked on a treatment against chemoresistant GTT. Our unprecedented clinical trial, TROPHIMMUM, demonstrated the efficacy of immunotherapy via an antibody, avelumab. Following these positive results, our intuition was that this immunotherapy could also work before the emergence of resistance in “low risk” GTT, as a complement to conventional chemotherapy ?, recounts Pr Benoit YOU.?

26 patients enrolled in France

In April 2020, the oncologist and Pr BOLZE launch the TROPHAMED study with the goal of observing the effects of associating immunotherapy (via the intravenous diffusion of avelumab) with chemotherapy (via the intramuscular injection of the drug methotrexate, usually used).

“With methotrexate alone, the cure rate of low-risk GTT was around 70%. The goal was to exceed this rate” emphasizes Pr BOLZE.

Safety was assessed with 6 patients who received a combination of immunotherapy and chemotherapy, which has never been done before. Once the safety phase was validated, Pr You and Pr Bolze triggered a phase II multi-centric trial. From 2020 to 2023, 26 voluntary patients were included from nine hospitals members of the National Reference centres for trophoblastic diseases’ network, and specialized in early-phase gynaecological clinical trials. “Without this unique coordination in the follow-up of patients with GTT, made possible by the French reference centre, this study could never have been conducted” points out Pr Jean-Pierre LOTZ, head of the Paris investigating centre.

“We are close to eradication of this form of pregnancy cancer”

Skilfully devised, the double-therapy set up for each patient is methodical: 1 injection of methotrexate every other day for a week, repeated every two weeks, and, on the first day of chemotherapy, 1 injection of avelumab (every two weeks). Then, the hCG level (Human Chorionic Gonadotropin, produced during pregnancy), is monitored every week. “As long as this hormone is present in abnormal levels, it indicates that the disease is still active. As soon as the level normalizes, we start the three last treatments, so six weeks, and then we stop all treatments” explains Pr You.

In May 2024, after the enrolment of the last patient Prs YOU and BOLZE discovered the unexpected result of TROPHAMET. “Initially, we were hoping for 85% cure rate so 22 patients. In the end, we managed to completely cure 25 out of the 26 patients, which represents 96%! Considering that we managed to cure 1 out of 2 patients with chemoresistant GTT with TROPHIMMUN, this means that we are not too far from total eradication of the entirety of gestational trophoblastic tumours. This is a considerable breakthrough, certainly the most important in the last 15 years in this type of pathology” is pleased to report Pr YOU.

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What are gestational trophoblastic diseases?

Originating from the cells that form the placenta during pregnancy, gestational trophoblastic diseases regroup a large spectre of benign or malignant pathologies that start in the uterus.

The most common form (1 in 1000 pregnancies in France) is hydatidiform mole. Initially benign, it resembles an early pregnancy but the embryo does not develop, only the placenta does. In 20% of the cases, it develops into a so-called “low-risk” gestational trophoblastic tumour (GTT), often metastatic and potentially fatal. More rarely, a GTT can develop after a normal delivery, and is generally classified as “high-risk”.

It is to treat these GTT, little-known by doctors and often misdiagnosed, that the Pr GOLFIER set up in 1999 the Trophoblastic Diseases Reference Centre at Lyon Sud Hospital, which has then been accredited as Rare Tumour Centre by the French National Cancer Institute.

Unique in France, it brings together healthcare professionals from a variety of disciplines (gynaecologists-obstetricians, oncologists, radiologists, anatomopathologists and biologists), whose collaboration has led to many significant breakthrough and international recognition over the past 25 years, with almost 15,0000 patients registered to date.

Version fran?aise ici : https://recherche.chu-lyon.fr/TROPHAMET