Exceptional Response to Erdafitinib in FGFR2-Mutated Metastatic Pancreatic Ductal Adenocarcinoma

Abstract

Despite advances in cancer therapeutics, pancreatic ductal adenocarcinoma (PDAC) remains among the deadliest malignancies, with a poor prognosis at time of diagnosis. Research in PDAC has suggested that adaptive signaling in the tumor microenvironment may promote tumor proliferation and survival. Several FGFR fusion genes—specifically FGFR2—are involved with the creation and progression of cancer. These mutations are found in a variety of cancer types. This report presents a unique case of a young patient with stage IV PDAC with a known FGFR2 fusion. This molecular alteration afforded a remarkable response to FGFR inhibitor therapy, erdafitinib, after the patient experienced disease progression on multiple chemotherapy regimens.

Genomic landscape of clinically advanced KRAS wild-type pancreatic ductal adenocarcinoma

“…A recent case report showed durable response of >12 months with erdafitinib in a young male with relapsed FGFR rearranged PDA. Incidentally, the patient in that particular case was also KRAS wild-type ( 52 ). The authors mention that the pathology revealed poorly differentiated adenocarcinoma, raising the possibility of it being a cholangiocarcinoma, as FGFR GA is more common in biliary tract cancers ( 52 , 53 ).…”

“…Incidentally, the patient in that particular case was also KRAS wild-type ( 52 ). The authors mention that the pathology revealed poorly differentiated adenocarcinoma, raising the possibility of it being a cholangiocarcinoma, as FGFR GA is more common in biliary tract cancers ( 52 , 53 ). FGFR2 GAs, which are mostly fusions, are found in 10-15% of intrahepatic cholangiocarcinoma’s ( 53 ), compared to 4.4% in our KRAS wild-type PDA cohort.…”

Expression of fibroblast growth factor receptor 1 correlates inversely with the efficacy of single‐agent fibroblast growth factor receptor‐specific inhibitors in pancreatic cancer

“…Promising pilot clinical studies have shown complete responses in small numbers of PDAC patients treated with pan‐FGFRi (Ng et al, 2022; Poon et al, 2021; Subbiah et al, 2022). Here we show that FGFR1 expression is a key factor in determining single‐agent pan‐FGFRi efficacy in PDAC.…”

“…Recent clinical case reports have shown complete responses of metastatic PDAC patients to single-agent FGFRi (Ng et al, 2022;Poon et al, 2021;Subbiah et al, 2022). However, the therapeutic utility of selective FGFRi in PDAC is largely unexplored.…”

“…It is specific for FGFRs 1–3, and has manageable clinical toxicity (Guagnano et al, 2011, 2012; Javle et al, 2018; Kelly et al, 2019; Nogova et al, 2017; Pal et al, 2018). Recent clinical case reports have shown complete responses of metastatic PDAC patients to single‐agent FGFRi (Ng et al, 2022; Poon et al, 2021; Subbiah et al, 2022). However, the therapeutic utility of selective FGFRi in PDAC is largely unexplored.…”