The presence of FGFR2 alterations occurs almost exclusively in intrahepatic cholangiocarcinoma (iCCA) and is observed in 10% to 16% of patients. One question discussed in abstracts over the past year has been whether alterations in FGFR2 affect survival in patients who receive systemic chemotherapy for iCCA.

After years of little progress on new treatments for patients with advanced cholangiocarcinoma, the FDA in 2020 approved the kinase inhibitor pemigatinib (Pemazyre, Incyte) for adult patients who have had 1 treatment for unresectable disease , locally advanced or metastatic with a FGFR2 merger or other rearrangement (FGFR2+), as determined by Foundation Medicine’s FoundationOne CDx companion diagnostic.

The presence of FGFR2 the alterations occur almost exclusively in intrahepatic cholangiocarcinoma (iCCA) and are seen in 10% to 16% of patients. A question explored in abstracts over the past year has been whether FGFR2 the alterations affect the survival of patients who receive systemic chemotherapy for iCCA.

At the 2021 American Society of Clinical Oncology Symposium on Gastrointestinal Cancers (ASCO GI), researchers from Memorial Sloan Kettering Cancer Center (MSKCC) and Weill Medical College presented data from the Clinical Database and MSKCC genomics to examine progression-free survival (PFS) and overall survival (OS) in patients with iCCA.1 Of the 132 patients included in the analysis, 15 were FGFR2+ and 115 were FGFR2-wild type. Among patients receiving first-line chemotherapy, the median PFS was 7.1 months for all patients; 6.2 months for FGFR2+ patients (15 patients) and 7.2 months for those FGFR2– wild type (107 patients). Among patients who had at least 2 prior lines of chemotherapy (90 patients, the median PFS of second-line chemotherapy was 5.6 months for FGFR2+ patients and 3.7 months for FGFR2-wild-type patients. The median OS was numerically longer in FGFR2+ patients compared to FGFR2-wild-type patients (31.3 months vs. 21.8 months). The authors of the data presented at ASCO concluded that patients receiving standard first-line systemic chemotherapy for iCCA had similar median PFS, regardless of FGFR2 status, but median PFS was longer in patients with FGFR2+ who received second-line therapy, and median OS was also longer in these patients.

At the ASCO annual meeting in May 2021, researchers from the University of Arizona and QED Therapeutics used real data from the Flatiron Health-Foundation Medicine CCA for a similar analysis, involving 571 patients and 270 clinics. oncology.2

The investigators said the primary goal was to “compare real-world OS in patients with advanced ACC and FGFR2 fusions/rearrangements compared to wild-type ones FGFR2 from the index date of diagnosis of advanced ACC until the date of death. A secondary objective, they wrote, was to analyze OS in patients with ACC and FGFR2 mergers/rearrangements from the start of second-line treatment until the date of death.

In May 2020, 75 of the patients had FGFR2 mergers/rearrangements; this group was 64% female, 95% had iCCA and 68% had stage IV disease at diagnosis. Of the 496 patients who were FGFR2-wild-type, 48% were female, 74% had iCCA and 55% were stage IV at diagnosis. Median OS from diagnostic index data was numerically higher, but not statistically different, for patients with FGFR2 fusions/rearrangements vs wild type FGFR2 (12.1 months versus 7.1 months). Investigators also found:

Of the 50 patients who were FGFR2+ received second-line treatment; median real-world OS from start of second-line therapy was 8.5 months.

The investigators concluded that these real-world OS results did not demonstrate a survival benefit for patients with ACC who were FGFR2+ vs wild type ones FGFR2 who received therapy for advanced disease. However, the OS trend favored patients who were FGFR2+. At the same time they write:FGFR2 status was not a significant predictor of OS after adjusting for potential prognostic covariates. »

The study is still examining OS from the start of second-line treatment in hospitalized patients with advanced ACC, comparing FGFR2+ and those of wild type FGFR2.

The references

1. Abou-Alfa GK, Bibeau K, Schultz N, et al. Effect of FGFR2 alterations in survival in patients receiving systemic chemotherapy for intrahepatic cholangiocarcinoma. J Clin Oncol. 2021;39(suppl_3). DOI: 10.1200/JCO.2021.39.3_suppl.303

2. Shroff RT, Avogadri F, Weng F, et al. Natural history of patients (pts) with advanced cholangiocarcinoma (CCA) with FGFR2 gene fusion/rearrangement or wild-type (WT) FGFR2. J Clin Oncol. 2021;39(suppl_15) abstract 4089. DOI: 10.1200/JCO.2021.39.15_suppl.4089

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