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The presence of FGFR2 alterations occurs almost exclusively in intrahepatic cholangiocarcinoma (iCCA) and is seen in 10% to 16% of patients. A question examined in abstracts over the past year has been whether FGFR2 alterations affect survival in those patients who receive systemic chemotherapy for iCCA.
After years of little progress on new treatments for patients with advanced cholangiocarcinoma, FDA in 2020 approved the kinase inhibitor pemigatinib (Pemazyre, Incyte) for adult patients who have had 1 treatment for unresectable, locally advanced or metastatic disease with an FGFR2 fusion or other rearrangement (FGFR2+), as determined by Foundation Medicine’s FoundationOne CDx companion diagnostic.
The presence of FGFR2 alterations occurs almost exclusively in intrahepatic cholangiocarcinoma (iCCA) and is seen in 10% to 16% of patients. A question examined in abstracts over the past year has been whether FGFR2 alterations affect survival in those patients who receive systemic chemotherapy for iCCA.
At the 2021 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI), investigators from Memorial Sloan Kettering Cancer Center (MSKCC) & Weill Medical College presented data from the clinical and genomic database at MSKCC to examine progression-free survival (PFS) and overall survival (OS) in patients with iCCA.1 Among the 132 patients included in the analysis, 15 were FGFR2+ and 115 were FGFR2-wild type. Among patients receiving first-line chemotherapy, 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 with at least 2 prior lines of chemotherapy (90 patients, median PFS second-line chemotherapy was 5.6 months for FGFR2+ patients and 3.7 months for FGFR2-wild type patients. Median OS was numerically longer in FGFR2+ patients compared with FGFR2-wild type patients (31.3 months vs 21.8 months). Authors of the data presented at ASCO concluded that patients receiving first-line standard systemic chemotherapy for iCCA had similar median PFS whether regardless of FGFR2 status, but median PFS was longer in patients with FGFR2+ who received second-line therapy, and median OS was longer in these patients as well.
At the May 2021 ASCO annual meeting, investigators from the University of Arizona and QED Therapeutics used real-world data from the Flatiron Health-Foundation Medicine CCA for a similar analysis, involving 571 patients and 270 cancer clinics.2
The investigators said the primary point was “to compare real-world OS in patients with advanced CCA and FGFR2 fusions/rearrangements vs. those with wild-type FGFR2 from the index date of diagnosis of advanced CCA to date of death.” A secondary objective, they wrote, was to analyze OS in those patients with CCA and FGFR2 fusions/rearrangements from the start of second-line therapy to date of death.
As of May 2020, 75 of the patients had FGFR2 fusions/rearrangements; this goup 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 at stage IV at diagnosis. Median OS from the index data of diagnosis was numerically higher, but not statistically different, for patients with FGFR2 fusions/rearrangements vs. wild-type FGFR2 (12.1 months vs. 7.1 months).Investigators also found:
Of the 50 patients who were FGFR2+ received second-line therapy; median real-world OS from the start of second-line therapy was 8.5 months.
Investigators concluded that these real-world OS findings did not demonstrate a survival advantage for patients with CCA who were FGFR2+ vs those with wild-type FGFR2 who received therapies for advanced disease. However, the OS trend favored those patients who were FGFR2+. At the same time, they wrote, “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 therapy inpatients with advanced CCA, comparing FGFR2+ and those with wild-type FGFR2.
References
1. Abou-Alfa GK, Bibeau K, Schultz N, et al. Effect of FGFR2 alterations on 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) abstr 4089. DOI: 10.1200/JCO.2021.39.15_suppl.4089
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