Pemigatinib provides durable responses and prolonged OS in previously treated patients with advanced or metastatic CCA and FGFR2 fusions or rearrangements

The phase 2 FIGHT-202 trial evaluated the safety and efficacy of pemigatinib in patients with previously treated locally advanced or metastatic cholangiocarcinoma (CCA) harbouring FGFR2 fusions or rearrangements. After a median follow-up of 45.4 months, pemigatinib continued to demonstrate durable responses with a prolonged OS in these patients. The safety profile continued to be manageable, without any new safety signals. These results further highlight the need for molecular testing in patients with CCA.

CCA is an aggressive epithelial tumour of the bile duct that has a poor prognosis. FGFR1-3 alterations are among the oncogenic drivers found in these genomically heterogeneous tumours.  Pemigatinib is an oral, potent, selective fibroblast growth factor receptor (FGFR) 1, 2, and 3 inhibitor that is approved for the treatment of adults with previously treated, unresectable locally advanced/metastatic CCA with an FGFR2 fusion or other rearrangement. During ESMO WCGI 2022, the final results were presented from an open-label, single-arm, multicentre phase 2 study evaluating the safety and efficacy of pemigatinib in patients with previously treated locally advanced or metastatic CCA.

Study design

Eligible patients were adults (≥18 years old), with locally advanced/metastatic or surgically unresectable CCA that progressed after ≥1 prior therapy, a documented FGF/FGFR status, Eastern Cooperative Oncology Group performance status ≤2, and an adequate hepatic/renal function. Patients were separated into three cohorts based on their FGF/FGFR status: patients with FGFR2 fusions or rearrangements were included in cohort A, patients with other genetic FGF/FGFR alterations were allocated to cohort B and patients without FGF/FGFR alterations were grouped in cohort C. All patients received 13.5 mg pemigatinib once daily (two weeks on/one week off) until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) in cohort A, while secondary objectives included the ORR in cohorts B, C and A/B combined, the duration of response (DoR), the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety across all cohorts.

Results

In total, 147 patients were enrolled (108 in cohort A, 20 in cohort B and seven in cohort C) in the study with a median age of 59 years. The median duration of follow-up was 45.4 months. In total, 98.6% of patients discontinued treatment, most commonly because of disease progression (n=105/147; 71.4%). In cohort A, the ORR was reported at 37.0% with a median DoR of 9.1 months. The DCR reached 82%, 40% and 18% for cohorts A, B and C, respectively. Complete responses were observed in 3% of patients in arm A, while there were no CRs in cohorts B and C. Partial response was observed in 34% of the patients in arm A, and 0% in arms B and C. Median PFS was 7.0 months for cohort A, and 2.1 and 1.5  months for cohorts B and C, respectively. Median OS was 17.5, 6.7, and 4.0 months for cohorts A, B and C. The safety profile remained consistent with the primary publication, and no new safety signals were observed. All patients reported treatment-emergent adverse events (TEAEs), with hyperphosphatemia (58%), alopecia (50%), and diarrhoea (48%) being the most common ones. Most TEAEs were grade 1 or 2. The most common grade ≥3 TEAE was hypophosphatemia (14.3%). Additionally, 91.8% of patients had a treatment-related AE, 4.1% had a fatal TEAE (all considered unrelated to pemigatinib treatment), and 10.2% discontinued pemigatinib due to a TEAE.

Conclusions

In the final analysis of FIGHT-202, pemigatinib continued to demonstrate durable responses, leading to a prolonged OS in patients with previously treated advanced or metastatic CCA with FGFR2 fusions or rearrangements. The safety profile continued to be manageable, without new safety signals. As such, these results further support the use of pemigatinib in this setting and underscore the importance of molecular testing in patients with CCA.

Reference

Vogel A, Sahai V, Hollebecque, A et al. Pemigatinib for previously treated locally advanced or metastatic cholangiocarcinoma: final results from FIGHT-202. Presented at ESMO WCGI 2022; Abstract O-2.