Second-Line Pemigatinib May Provide PFS Benefit in Cholangiocarcinoma With FGFR2 Fusions/Rearrangements

Kristen Bibeau, MSPH, PhD

Second-line treatment with pemigatinib (Pemazyre) may be linked with prolonged progression-free survival (PFS) compared with other systemic therapies in patients with cholangiocarcinoma harboring FGFR2 fusions or rearrangements, according to data from a post-hoc analysis of the phase 2 FIGHT-202 trial (NCT02924376) published in the JCO Precision Oncology.¹

Among 65 patients with FGFR2 fusion– or rearrangement–positive cholangiocarcinoma who progressed after 1 line of prior systemic therapy, second-line pemigatinib resulted in a median PFS of 7.0 months (95% CI, 4.9-11.1) compared with 4.2 months (95% CI, 3.0-5.3) in those with FGFR2 fusions/rearrangements (n = 39) who received second-line systemic therapy.

In patients with other FGF/FGFR alterations (n = 12), second-line pemigatinib resulted in a median PFS of 2.1 months (95% CI, 1.2-6.9) compared with 3.0 months (95% CI, 1.1-9.9) with second-line systemic therapy (n = 8). In those without FGF/FGFR alterations, second-line pemigatinib (n = 12) resulted in a median PFS of 1.7 months (95% CI, 1.2-2.0) vs 5.9 months (95% CI, 2.4-12.5) with second-line systemic therapy (n = 6).

The median PFS achieved with first-line systemic therapy was 5.5 months (95% CI, 4.0-8.0), 4.4 months (95% CI, 2.7-7.1), and 2.8 months (95% CI, 1.6-11.3) in patients with FGFR2 fusions/rearrangements (n = 102), other FGF/FGFR alterations (n = 19), or no FGF/FGFR alterations (n = 16), respectively.

“These data suggest that pemigatinib is associated with a meaningful clinical benefit over other systemic therapy, predominantly chemotherapy, in the second-line setting for patients with advanced or metastatic cholangiocarcinoma harboring FGFR2 fusions or rearrangements,” lead study author Kristen Bibeau, MSPH, PhD, executive director and head of Global Epidemiology and RWE Statistics at Incyte, and colleagues, wrote in the paper.

Surgical resection represents the only current curative option for patients with cholangiocarcinoma; however, since most patients are diagnosed with advanced disease, many are ineligible for resection.² After first-line gemcitabine/cisplatin, no standard of care has been established for the second- or later-line settings.

Pemigatinib was evaluated in FIGHT-202 as a potential treatment for patients with locally advanced or metastatic cholangiocarcinoma who received at least 1 line of prior therapy. Patients enrolled to the trial had their FGF/FGFR status centrally confirmed and were required to have adequate renal function.

The single-arm trial divided patients into 3 cohorts: those with FGFR2 fusions/rearrangements (cohort A), those with other FGF/FGFR alterations (cohort B), and those with no FGF/FGFR alterations (cohort C). All patients received 13.5 mg of oral pemigatinib once daily on a 2-week-on, 1-week-off schedule.

The primary end point of the trial was objective response rate (ORR) in the cohort of patients with FGFR2 fusions/rearrangements. A key secondary end point was ORR in patients with other FGF/FGFR alterations, those with all FGF/FGFR alterations, and those without FGFR alterations served as secondary end points. PFS and safety served as other secondary end points.

Prior data from FIGHT-202 showed that patients with cholangiocarcinoma harboring FGFR2 fusions or rearrangements (n = 108) achieved an ORR of 37% (95% CI, 27.9%-46.9%) with pemigatinib, which included 4 complete responses and 36 partial responses.³ The median PFS was 7.0 months (95% CI, 6.1-10.5), and the median overall survival (OS) was 17.5 months (95% CI, 14.4-22.9).

These data led to the April 2020 FDA approval of pemigatinib for the treatment of patients with previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements.⁴

The primary objective of the post-hoc analysis was PFS in patients with FGFR2 fusions/rearrangements.

The median ages in cohorts A (n = 107), B (n = 20), and C (n = 18) were 54.5 years (range, 25-76), 61.3 years (range, 44-77), and 64.2 years (range, 30-77), respectively. The most common systemic therapies received prior to enrollment on the trial included pyrimidine analogs (99.3%) and platinum compounds (93.8%). Additionally, gemcitabine plus cisplatin (77.9%) was the most common combination regimen received, and this was primarily received in the first line (67.6%). Across all lines, gemcitabine was received as monotherapy in 6.9% of patients, and no patients received single-agent cisplatin.

Among patients with FGFR2 fusions/rearrangements, 67.6% received a prior combination regimen that included gemcitabine plus cisplatin in the first line, the median PFS was 5.7 months (95% CI, 4.6-9.1) vs 4.1 months (95% CI, 2.3-6.5) in those who received any other first-line regimen prior to trial enrollment. The median PFS achieved with first-line gemcitabine/cisplatin was 3.9 months (95% CI, 1.6-6.4) and 2.8 months (95% CI, 1.6-17.7) in patients with other FGF/FGFR alterations (n = 12) and those without FGF/FGFR alterations (n = 13), respectively.

Notably, 93% of 41 patients with FGFR2 fusions/rearrangements received second-line chemotherapy, which included gemcitabine plus cisplatin (17%), 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX; 17%), or fluorouracil plus oxaliplatin (12%). The remaining 3 patients received second-line anti–PD-1 or targeted therapy in the form of nivolumab (Opdivo), pazopanib (Votrient), or ponatinib (Iclusig).

Study authors noted the importance of genomic testing for patients with cholangiocarcinoma to identify those who could benefit from targeted therapy.

“Further research is warranted to prospectively characterize the disease course and response to chemotherapy in patients with and without FGFR2 fusions and, in the real-world setting, to characterize the second-line treatment outcomes of patients with FGFR2 alterations outside of a clinical trial,” the study authors concluded.

References

1. Bibeau K, Féliz L, Lihou CF, Ren H, Abou-Alfa GK. Progression-free survival in patients with cholangiocarcinoma with or without FGF/FGFR alterations: a FIGHT-202 post hoc analysis of prior systemic therapy response. JCO Precis Oncol. Published online on April 6, 2022. doi:10.1200/PO.21.00414
2. Khan SA, Davidson BR, Goldin RD, et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Gut. 2012;61(12):1657-1669. doi:10.1136/gutjnl-2011-301748
3. Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated locally advanced/metastatic cholangiocarcinoma (CCA): update of FIGHT-202. J Clin Oncol. 2021;39(suppl 15):4086. doi:10.1200/JCO.2021.39.15_suppl.4086
4. FDA approves first targeted treatment for patients with cholangiocarcinoma, a cancer of bile ducts. News release. FDA. April 17, 2020. Accessed May 24, 2022. https://prn.to/2xGXrO6