Prognostic Value of FGFR2 Alterations in Patients Receiving Systemic Chemotherapy for Intrahepatic CCA

A retrospective analysis indicated the prognostic value of FGFR2 fusions/rearrangements in patients with intrahepatic CCA receiving systemic chemotherapy, which warrants additional study.

To understand the effects of FGFR2 status on response to systemic chemotherapy, a retrospective analysis evaluated survival outcomes among patients receiving standard systemic chemotherapy for intrahepatic cholangiocarcinoma (iCCA) who harbor FGFR2 fusions/rearrangements (FGFR2-positive) or wild-type FGFR2.

The retrospective analysis used clinical and genomic data from the Memorial Sloan Kettering Cancer Center (New York, NY) genomic profiling database for all patients with iCCA. Median progression-free survival (PFS; calculated from the initial dose of first-line chemotherapy until progression, death, or last visit) and overall survival (OS; calculated from diagnosis until death) were computed.

The current analysis included a total of 132 patients with iCCA. The median age of all patients at diagnosis was 62.0 years. Overall, 54.5% of the participants were female; 53.8% had stage IV disease, 93.0% had received platinum-based first-line therapy, and 59.6% had received pyrimidine-based chemotherapy. Of the 132 patients, 115 patients had no FGFR2 alterations (wild-type FGFR2), 15 had FGFR2 fusions/rearrangements (FGFR2-positive), and 2 had other FGFR2 alterations. Patients in the FGFR2-positive cohort were younger at diagnosis and were more likely to have received >3 lines of therapy compared with the wild-type FGFR2 cohort.

Since initiation of standard first-line chemotherapy, median PFS was comparable in the overall, FGFR2-positive, and wild-type FGFR2 cohorts (7.1 months, 6.2 months, and 7.2 months, respectively). Among patients who received second-line chemotherapy (n = 90), median PFS was relatively longer in the FGFR2-positive cohort than in the wild-type FGFR2 cohort (5.6 months [n = 8] vs 3.7 months [n = 81], respectively). Median OS since diagnosis was numerically longer in the FGFR2-positive cohort compared with the wild-type FGFR2 cohort (31.3 months [n = 9] vs 21.8 months [n = 115], respectively), as was the median OS since the start of second-line therapy (23.2 months [n = 4] vs 8.7 months [n = 76], respectively).

Findings from this retrospective analysis suggest that median OS following both first-line and second-line chemotherapy, and PFS following second-line therapy, may be longer in patients who harbor FGFR2 fusions/rearrangements compared with those with no FGFR2 alterations, warranting further research on the prognostic value of FGFR2 fusion–driven iCCA.

Source: Abou-Alfa G, 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):303-303.