Progression-Free Survival in Patients With Cholangiocarcinoma With or Without FGF/FGFR Alterations: A FIGHT-202 Post Hoc Analysis of Prior Systemic Therapy Response

Abstract

PURPOSE Oncogenic fibroblast growth factor receptor (FGFR) gene alterations have been described in patients with cholangiocarcinoma (CCA). This post hoc analysis assessed progression-free survival (PFS) in patients who had received first- or second-line systemic therapy for advanced/metastatic CCA before enrollment in the phase II FIGHT-202 study (ClinicalTrials.gov identifier: NCT02924376 ). PATIENTS AND METHODS Patients with locally advanced or metastatic CCA with FGFR2 fusions/rearrangements (n = 107), other FGF/FGFR alterations (n = 20), or no FGF/FGFR alterations (n = 18) and documented disease progression after at least one systemic cancer therapy before enrollment in FIGHT-202 were assessed. Prior therapy and disease response data were collated from electronic case report forms. PFS was calculated for each prior line of systemic cancer therapy. RESULTS Among patients with FGFR2 fusions/rearrangements, other FGF/ FGFR alterations, and no FGF/ FGFR alterations, respectively, the median PFS with prior first-line systemic therapy was 5.5 months (95% CI, 4.0 to 8.0; n = 102), 4.4 months (2.7 to 7.1; n = 19), and 2.8 months (1.6 to 11.3; n = 16); the median PFS with prior second-line systemic therapy was 4.2 months (3.0 to 5.3; n = 39), 3.0 months (1.1 to 9.9; n = 8), and 5.9 months (2.4 to 12.5; n = 6). The median PFS was 7.0 months (4.9 to 11.1) for patients with FGFR2 fusions/rearrangements (n = 65) with second-line pemigatinib received during the FIGHT-202 trial. CONCLUSION In patients with CCA and FGFR2 fusions or rearrangements, second-line treatment with pemigatinib may be associated with longer PFS compared with second-line treatment with systemic therapy received before study enrollment; however, a prospective controlled trial is required to confirm this. The results support the therapeutic potential of pemigatinib previously demonstrated in FIGHT-202.

Effect of FGFR2 Alterations on Overall and Progression-Free Survival in Patients Receiving Systemic Therapy for Intrahepatic Cholangiocarcinoma

“…Despite the observation that patients with FGFR2 fusions receiving second-line systemic therapy have longer PFS compared with patients with no FGFR2 alterations, PFS appears to be further improved by treatment with FGFR inhibitors. Recently updated data from FIGHT-202 in patients with CCA who received pemigatinib in second-line therapy showed a median PFS of 7.0 months for patients with FGFR2 fusions or rearrangements [ 39 ]. In a pivotal phase II study, infigratinib was associated with a median PFS of 7.3 months in 108 patients with FGFR2 fusions or rearrangements who had previously received one or more lines of therapy [ 28 ].…”

Molecular pathology for cholangiocarcinoma: a review of actionable genetic targets and their relevance to adjuvant & neoadjuvant therapy, staging, follow-up, and determination of minimal residual disease

“…Post-hoc analysis of the FIGHT-202 trial revealed that patients who received second-line treatment with pemigatinib had longer mPFS and better response rates compared to patients who received second-line systemic therapy prior to trial enrollment, suggesting that earlier treatment is key for optimizing clinical efficacy (22). Three phase III trials are currently underway to compare futibatinib (FOENIX-CCA3, NCT04093362), infigratinib ( P R O O F 3 0 1 , N C T 0 3 7 7 3 3 0 2 ) , a n d p e m i g a t i n i b (FIGHT-302, NCT03656536) as first-line monotherapy against current standard of care gemcitabine/cisplatin.…”

Role of Basic Fibroblast Growth Factor in Cancer: Biological Activity, Targeted Therapies, and Prognostic Value

“…Many of these clinical trials aim to evaluate progression-free survival (FPS), tolerability, and safety. The clinical trials reported in Table 2 show the inhibition of FGFR in different types of cancer, such as in cholangiocarcinoma [ 214 , 215 , 216 ]; in these studies, selective inhibitors of FGFR 1-4 were used, such as Futibatinib and Pemigatinib, demonstrating their efficacy. Regarding the safety, the most common adverse effect of the use of such drugs is hyperphosphatemia, probably attributable to the function of FGF23 and FGFR signaling in phosphate homeostasis.…”