PFS to Systemic Therapy in Patients with CCA with FGFR2 Fusions or Rearrangements

2020 Year in Review - Cholangiocarcinoma —December 20, 2020

Post-hoc analysis of the phase 2 FIGHT-202 study showed that second-line pemigatinib treatment resulted in a numerically longer PFS than standard systemic second-line treatment in patients with previously treated advanced/metastatic CCA.

There are limited data available on correlation of FGFR2 genetic alterations with treatment outcomes to systemic cancer therapy in the second-line metastatic setting. FIGHT-202 is a single-arm, phase 2 clinical trial of pemigatinib (Pemazyre), a selective, oral FGFR1-3 inhibitor, in patients with previously treated advanced/metastatic CCA (NCT02924376) who had progressed on ≥1 previous therapies. The objective of this post-hoc analysis of the FIGHT-202 study was to evaluate progression-free survival (PFS) on second-line systemic therapy received prior to study enrollment in patients with CCA harboring FGFR2 fusions or rearrangements. The results of this analysis were presented at the American Society of Clinical Oncology 2020 Gastrointestinal Cancers Symposium and summarized here.

In the FIGHT-202 study, eligible adults with disease progression after ≥1 previous treatments and documented FGF/FGFR gene status were assigned to cohort A (FGFR2 gene rearrangements/fusions), cohort B (other FGF/FGFR gene alterations), or cohort C (no FGF/FGFR gene alterations), and received oral pemigatinib 13.5 mg once daily for a 21-day cycle (2 weeks on, 1 week off) until disease progression or unacceptable toxicity. The primary end point was centrally confirmed objective response rate of cohort A. Secondary end points were overall response rate (cohorts B, A plus B, and C), duration of response, disease control rate, PFS, overall survival, and safety. For the post-hoc analysis, case report forms were reviewed to determine disease history and exposure to previous lines of systemic cancer therapies in the advanced setting before receiving pemigatinib. Median PFS was calculated using the Kaplan-Meier method.

In the post-hoc analysis, 102 patients who had received systemic therapy prior to study enrollment were included, with a median age of 54.5 years. The patients with FGFR fusions or rearrangements tended to be younger at the time of diagnosis and were diagnosed at an earlier tumor stage compared with those with no FGFR2 alterations. Among 69 patients with CCA with FGFR2 fusions/rearrangements that received first-line gemcitabine plus cisplatin chemotherapy who were subsequently enrolled in the FIGHT-202 study, median PFS was 5.7 months (95% CI, 4.6-9.1), which was deemed comparable to reported literature in an unselected population. Among the 39 patients with CCA with FGFR2 fusions/rearrangements who had received ≥2 previous second-line systemic therapies before enrolling in the FIGHT-202 study, median PFS was 4.2 months (95% CI, 3.0-5.3). Among the 65 patients who had 1 line of previous therapy and received pemigatinib as their second-line therapy in the FIGHT-202 study, median PFS was 7.0 months (95% CI, 4.9-11.1).

These results suggest that, for patients with CCA harboring FGFR2 fusions or rearrangements, second-line treatment with pemigatinib results in a numerically longer PFS than standard systemic second-line treatment albeit the retrospective nature of the analysis and that clinical trial participants may not truly reflect a general CCA patient population. Further research is warranted to characterize the second-line treatment outcomes of patients with FGFR2 alterations in the real-world setting.

Source: Bibeau K, et al. J Clin Oncol. 2020;38(4_suppl). Abstract 588.

Last modified: March 11, 2021

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