Erdafitinib Data in FGFR+ Cholangiocarcinoma Indicates Utility of NGS in Treatment Selection

Results from the phase 2 RAGNAR trial (NCT04083976) not only support the use of the FGFR inhibitor erdafitinib (Balversa) in the treatment of adults with advanced or metastatic FGFR-mutatedcholangiocarcinoma but emphasize the importance of identifying these alterations with next-generation sequencing (NGS), according to Shubham Pant, MD, MBBS.

Erdafitinib gained FDA approval in 2019 for adult patients with locally advanced or metastatic urothelial carcinoma and FGFR3/2 mutations, according to data from the phase 2 BLC2001 (NCT02365597) study. The agent is being investigated in other FGFR-mutant advanced solid tumors.¹

Previously reported interim results from the RAGNAR trial showed that erdafitinib elicited an overall response rate (ORR) of 41.9% in patients with cholangiocarcinoma and was well tolerated in all patients with advanced solid tumors and FGFR mutations or fusions who progressed on standard systemic therapies.²

Expansion cohort data from the RAGNAR trial were presented at the 2023 Gastrointestinal Cancers Symposium. The ORR was 60.0% (95% CI, 42.1-76.1) with erdafitinib, and median time to onset of response was 1.5 months (1.1-8.2). Safety data were consistent with the known adverse event (AE) profile of erdafitinib. A total 71.4% of patients with cholangiocarcinoma experienced grade 3 or higher treatment-emergent adverse events (TEAEs), with 8.6% discontinuing treatment due to AEs.³

“Next-generation sequencing [can help us choose between] the targeted therapies currently available…[for this] genomically rich disease,” said Pant, who is an associate professor in the Departments of Investigational Cancer Therapeutics and of Gastrointestinal Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston.

In an interview with OncLive®, Pant discusses significant efficacy and safety data from the RAGNAR trial, how erdafitinib fits into the current treatment paradigm for biliary tract cancers, and the role of NGS in the selection of FGFR inhibitors for this patient population.

OncLive^®: Please provide some background on the RAGNAR trial design.

Pant: [The cohort consisted of] 35 patients with cholangiocarcinoma and an FGFR fusion or mutation. [FGFR] is normally one of the driver mutations [in this tumor type]. Patients were heavily pretreated; about 67% patients had received more than 2 lines of therapy, [while] about 33% of patients [had] received 1 line of therapy or more.

We [treated patients with] a targeted therapy called erdafitinib, [which] is already approved in bladder cancer, but [is often] used in cholangiocarcinoma. We [wanted] to see the effects of this targeted therapy in that patient population, and [potentially] improve the treatment options for our patients with these targeted therapies.

What efficacy and tolerability data were reported from this study?

At the [Gastrointestinal Cancers Symposium], we presented [data on a cohort of patients with cholangiocarcinoma [from] a [large] tumor-agnostic basket trial. Interim analysis [of] this basket trial was [previously] presented at the 2022 ASCO Annual Meeting.

We had a centrally confirmed ORR of up to 60%. [This] means that 60% of patients had more than a 30% reduction in the sum of target lesions. Disease control rate [was] 100% in these patients, [which] was encouraging to see. The main side [adverse events (AEs)] that we saw in this patient population [were] hyperphosphatemia, stomatitis, or mouth ulcers. [These AEs] are commonly seen with other FGFR inhibitors and with erdafitinib [in] other malignancies.

How can results from this investigation impact current practice? What future research efforts will occur based on this research?

Other FGFR inhibitors have gotten accelerated approval [for intrahepatic cholangiocarcinoma] are pemigatinib [Pemazyre] and futibatinib [Lytgobi]. More data [on erdafitinib] will come out later this year, and we hope [that it will support] erdafitinib as another potential option [for] patients.

We will continue longer follow[-up] of these patients [to] see if the duration of response and progression-free survival rate of 8.4 months [increases]. We would [also] like to see if any combination strategies would be of further benefit to our patients later [in treatment].

What does this research reveal about the importance of sequencing in biliary tract cancer?

Our main takeaway is that patients [with] biliary tract cancer need to advocate for themselves. Biliary tract cancer is a genomically rich disease, [with many] targeted therapy options. [These patients] need to have NGS to find [the best therapy]. Just like we all have different fingerprints, every tumor [has] a different fingerprint. Patients with biliary tract cancers can have FGFR fusions or mutations, IGF1 mutations, or HER2 overexpression. NGS potentially [allows us to administer] drugs which are already approved or are in clinical trials.

Editor’s Note: Dr. Pant has a consulting or advisory role at 4D Pharma, Ipsen, Janssen, Novartis, Xencor, and Zymeworks.

References

1. FDA grants accelerated approval to erdafitinib for metastatic urothelial carcinoma. News release. FDA; April 12, 2019. Accessed January 25, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/
2. Loriot Y, Schuler MH, Iyer G, et al. 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. J Clin Oncol. 2022;40:16s(suppl; abstr 1005). doi:10.1200/JCO.2022.40.16_suppl.3007
3. Pant S, Schuler MH, Iyer G, et al. Efficacy and safety of erdafitinib in adults with cholangiocarcinoma (CCA) with prespecified fibroblast growth factor receptor alterations (FGFRalt) in the phase 2 open-label, single-arm RAGNAR trial: expansion cohort results. J Clin Oncol. 2023;41(suppl 4; abstr 610). doi:10.1200/JCO.2023.41.4_suppl.610