FGFR inhibitors

The multicenter, open-label, single-arm phase II FIGHT-202 trial (NCT02924376) enrolled 147 patients with disease progression during or after at least one previous therapy. A total of 108 patients had FGFR2 rearrangements or fusions. All patients received 13.5 mg of pemigatinib orally once daily for 14 consecutive days, followed by 7 days off therapy. At a median follow-up of 45.4 months, the following results were observed:[20][Level of evidence C3]In 2020, the FDA granted accelerated approval of pemigatinib for the treatment of adults with previously treated unresectable or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement.

The multicenter, open-label, single-arm phase II FIGHT-202 trial (NCT02924376) enrolled 147 patients with disease progression during or after at least one previous therapy. A total of 108 patients had FGFR2 rearrangements or fusions. All patients received 13.5 mg of pemigatinib orally once daily for 14 consecutive days, followed by 7 days off therapy. At a median follow-up of 45.4 months, the following results were observed:[20][Level of evidence C3]In 2020, the FDA granted accelerated approval of pemigatinib for the treatment of adults with previously treated unresectable or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement.

The overall response rate in the cohort of patients with FGFR2 rearrangements/fusions was 37% (95% CI, 27.9%−46.9%), including three complete responses. Among the 40 patients who achieved an objective response, the median duration of response was 9.1 months (95% CI, 6.0–14.5).

The multicenter, open-label, single-arm phase II FIGHT-202 trial (NCT02924376) enrolled 147 patients with disease progression during or after at least one previous therapy. A total of 108 patients had FGFR2 rearrangements or fusions. All patients received 13.5 mg of pemigatinib orally once daily for 14 consecutive days, followed by 7 days off therapy. At a median follow-up of 45.4 months, the following results were observed:[20][Level of evidence C3]In 2020, the FDA granted accelerated approval of pemigatinib for the treatment of adults with previously treated unresectable or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement.

The median PFS in patients with FGFR2 rearrangements or fusions was 7.0 months (95% CI, 6.1–10.5), and the median OS was 17.5 months (95% CI, 14.4–22.9). Given the single-arm study design, the relative effect of pemigatinib on PFS and OS was not established. However, in the cohort of study patients whose tumors did not harbor FGFR rearrangements, the median PFS was only 1.5 months and the median OS was only 4.0 months.

The multicenter, open-label, single-arm phase II FIGHT-202 trial (NCT02924376) enrolled 147 patients with disease progression during or after at least one previous therapy. A total of 108 patients had FGFR2 rearrangements or fusions. All patients received 13.5 mg of pemigatinib orally once daily for 14 consecutive days, followed by 7 days off therapy. At a median follow-up of 45.4 months, the following results were observed:[20][Level of evidence C3]In 2020, the FDA granted accelerated approval of pemigatinib for the treatment of adults with previously treated unresectable or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement.

The most common adverse effect was hyperphosphatemia, occurring in 58.5% of patients, although no adverse effect was grade 3 or higher. Adverse events led to treatment discontinuation in 10.2% of patients, dose reduction in 13.64% of patients, and dose interruptions in 42.2% of patients.

Futibatinib is an irreversible noncompetitive inhibitor of FGFR1–4. Preclinical in vitro studies showed that futibatinib was less susceptible to on-target resistance variants than pemigatinib. However, there are no head-to-head clinical trial data comparing outcomes for the various FGFR inhibitors. The multinational, open-label, single-group, phase II FOENIX-CCA2 trial (NCT02052778) evaluated futibatinib in patients with previously treated intrahepatic cholangiocarcinoma and FGFR2 fusions or rearrangements. The study enrolled 103 patients with disease progression after at least one previous line of systemic therapy. All patients received futibatinib at a continuous dose of 20 mg once daily.[21][Level of evidence C3]

Futibatinib is an irreversible noncompetitive inhibitor of FGFR1–4. Preclinical in vitro studies showed that futibatinib was less susceptible to on-target resistance variants than pemigatinib. However, there are no head-to-head clinical trial data comparing outcomes for the various FGFR inhibitors. The multinational, open-label, single-group, phase II FOENIX-CCA2 trial (NCT02052778) evaluated futibatinib in patients with previously treated intrahepatic cholangiocarcinoma and FGFR2 fusions or rearrangements. The study enrolled 103 patients with disease progression after at least one previous line of systemic therapy. All patients received futibatinib at a continuous dose of 20 mg once daily.[21][Level of evidence C3]

The overall response rate was 42% (95% CI, 31.1%–50.4%), including one complete response. Of the patients who had a response, the median duration of response was 9.7 months.

Futibatinib is an irreversible noncompetitive inhibitor of FGFR1–4. Preclinical in vitro studies showed that futibatinib was less susceptible to on-target resistance variants than pemigatinib. However, there are no head-to-head clinical trial data comparing outcomes for the various FGFR inhibitors. The multinational, open-label, single-group, phase II FOENIX-CCA2 trial (NCT02052778) evaluated futibatinib in patients with previously treated intrahepatic cholangiocarcinoma and FGFR2 fusions or rearrangements. The study enrolled 103 patients with disease progression after at least one previous line of systemic therapy. All patients received futibatinib at a continuous dose of 20 mg once daily.[21][Level of evidence C3]

The median PFS was 9 months (95% CI, 6.9–13.1), and the median OS was 21.7 months (95% CI 14.5–NR). Given the single-arm study design, the relative effect of futibatinib on PFS and OS has not yet been established.

Futibatinib is an irreversible noncompetitive inhibitor of FGFR1–4. Preclinical in vitro studies showed that futibatinib was less susceptible to on-target resistance variants than pemigatinib. However, there are no head-to-head clinical trial data comparing outcomes for the various FGFR inhibitors. The multinational, open-label, single-group, phase II FOENIX-CCA2 trial (NCT02052778) evaluated futibatinib in patients with previously treated intrahepatic cholangiocarcinoma and FGFR2 fusions or rearrangements. The study enrolled 103 patients with disease progression after at least one previous line of systemic therapy. All patients received futibatinib at a continuous dose of 20 mg once daily.[21][Level of evidence C3]

The most common adverse effect of any grade was hyperphosphatemia, which occurred in 85% of patients and was grade 3 in 30% of patients. Other common adverse effects included alopecia (33%), dry mouth (30%), dry skin (27%), and fatigue (25%). Other notable grade 3 toxicities included aspartate aminotransferase elevation (7%) and stomatitis (6%). Treatment-related adverse events led to dose interruptions in 50% of patients, dose reductions in 54% of patients, and permanent drug discontinuation in 2% of patients.