ASCO 2022 - RAGNAR study: the benefits of targeted therapy beyond bladder cancer

ASCO 2022

RAGNAR study: the benefits of targeted therapy beyond bladder cancer

Erdafitinib is a novel targeted therapy that has already been approved in a number of countries for the treatment of bladder cancer carrying certain mutations or fusion of the FGFR2/3 genes. The RAGNAR study is the first to demonstrate that this agent might also be useful in some twenty advanced stage cancers and rare tumours carrying mutations or fusions of FGFR genes (1 to 4). This agent, which is generally well tolerated, by producing a response rate of almost 30% and a disease control figure of 70%, allows us to conceive of its being helpful in quite a wide range of conditions in the near future. The intermediate results of this trial were presented orally at the American Society of Clinical Oncology (ASCO) on the 7^th June by Dr Yohann Loriot, Deputy Head of the Drug Development Department and Head of the Genitourinary Oncology Team at Gustave Roussy.

Abstract No. 3007 presented in oral session Tuesday 7th June at 6.57 pm

The tumour-agnostic approach in oncology does not depend on the site of the tumour but on identical molecular profiles found in certain patients. In other words, the therapy is not directed against the type of cancer but rather towards the genetic changes. The RAGNAR study was designed with this purpose by basing it entirely on abnormalities in the FGFR 1, 2, 3 and 4 genes. These genetic mutations are found in a wide variety of cancers, involving 2% of gliomas, 15 to 20% of urothelial carcinomas (bladder cancer), 8% of cholangiocarcinomas (biliary tract cancers) and less than 1% of cancers of the lung and kidney and those of the uterine cervix and of colon and rectum.

Erdafitinib is the first targeted therapy to be authorised in the United States and 13 other countries for use in advanced bladder cancer. It is an oral FGFR inhibitor targeting mutations and fusions in these genes. Dr Loriot, Deputy Head of the Drug Development Department at Gustave Roussy and lead investigator on the RAGNAR study, followed up the convincing bladder cancer findings by initiating an international study to assess the safety and efficacy of this new agent in other cancers and diseases with the same genetic mutations.

Benefits in some fifteen advanced cancers

The RAGNAR international study recruited 178 patients (200 for completion) aged over 6 years with a variety of solid tumours (kidney, breast, salivary glands, pancreas, lung, gastric cancer, low and high grade gliomas, endometrium, etc.) including rare ones. A mutation or fusion of one of the FGFR genes was present. Over three quarters of the patients had metastases in solid organs and 40% of them had previously received at least 3 types of treatments. All of those recruited had exhausted standard therapies before being enrolled in the trial. 

Erdafitinib was administered daily via the oral route as long as the medication was well tolerated and effective.  

“The objective response rate, assessed by an independent review committee, was 29% with a disease control value of over 70%. The median duration of the response was 7 months. A large number of tumours may be responsive to this agent. This applies to cholangiocarcinomas (8% of the patients studied), and to tumours that are difficult to treat such as pancreatic cancer, tumours of salivary glands, tumours of undetermined origin, breast cancer, high grade gliomas, lung and gastric cancers, etc. The response rate is very variable,” explained Dr Loriot.

Intermediate analysis of RAGNAR also showed that erdafitinib was well tolerated and that the side effect profile was similar to that seen in bladder cancer studies. Some known reversible side effects (hyperphosphataemia, hand-foot syndrome and retinopathies) were observed and were managed by symptomatic measures and reduction in dose.

These findings allow us to conceive of this new targeted therapy being helpful in quite a wide range of conditions in the near future. The substantive analysis is expected to take place in late 2022.

Abstract No. 3007
Tumor agnostic efficacy and safety of erdafitinib in patients (pts) with advanced solid tumors with prespecified fibroblast growth factor receptor alterations (FGFRalt) in RAGNAR: Interim analysis (IA) results
Oral abstract session
Tuesday 7^th June 2022 | 18:57 – 19:09 UTC+2