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First-line pemigatinib (Pemazyre) significantly prolonged progression-free survival (PFS) compared with gemcitabine plus cisplatin in patients with unresectable, locally advanced, or metastatic cholangiocarcinoma harboring FGFR2 rearrangements, according to data from the phase 3 FIGHT-302 trial (NCT03656536) presented at the
Findings demonstrated that pemigatinib (n = 83) yielded a median PFS of 8.34 months (95% CI, 6.51-12.22) vs 6.80 months (95% CI, 6.05-8.25) with gemcitabine plus cisplatin (n = 84; HR, 0.584; 95% CI, 0.393-0.868; P = .0078) at median follow-ups of 42.1 and 42.9 months, respectively.
“Results support potential consideration of pemigatinib in the first-line setting for patients with FGR2-rearranged cholangiocarcinoma,” lead study author Tanios S. Bekaii-Saab, MD, said in a presentation of the data. “Additionally, these results confirm the use of pemigatinib following disease progression on chemotherapy for FGFR2-rearranged cholangiocarcinoma.”
Bekaii-Saab is the David F. and Margaret T. Grohne Professor of Novel Therapeutics for Cancer Research I at the Mayo Clinic College of Medicine and Science; division chair of the Hematology/Medical Oncology at Mayo Clinic in Phoenix, Arizona; co-leader of the Advanced Clinical and Translational Science Program and the Disease Group leader for Gastrointestinal Cancers for the Mayo Clinic Comprehensive Cancer Center; co-leader of the Hepatobiliary Cancer Sub-Committee of the Alliance for Clinical Trials in Oncology; and the co-chair for the National Cancer Institute’s Hepatobiliary Task Force.
Pemigatinib is
FIGHT-302 was an international, open-label, randomized, active-controlled trial that enrolled patients with confirmed unresectable, locally advanced, or metastatic cholangiocarcinoma with documented FGFR2 rearrangements.2
Notably, patients were allowed to received 1 cycle of gemcitabine plus cisplatin if they were in urgent need of treatment.
Investigators prescreened 4563 patients for FGFR2 rearrangements, of whom 196 were ultimately screened. Ultimately, 167 patients were enrolled and randomly assigned 1:1 to receive oral pemigatinib at 13.5 mg once per on a 21-day cycle or gemcitabine at 1000 mg/m² plus cisplatin 25 mg/m² intravenously on days 1 and 8 of each 21-day cycle for up to 8 cycles.
PFS per independent central review served as the trial’s primary end point. Key secondary end points included disease control rate (DCR), duration of response (DOR), overall response rate (ORR), overall survival (OS), and safety.
The median age was 61 years (range, 25-82) in the pemigatinib arm vs 59.5 years (range, 28-79) in the chemotherapy arm. Most patients were female (pemigatinib, 55.4%; chemotherap, 60.7%), White (72.3%; 67.9%), had an ECOG performance status of 0 (65.1%; 63.1%), were from a Western region (86.7%; 84.5%), had distant metastases (78.3%; 78.6%), and had intrahepatic disease (98.8%; 96.4%).
Notably. 13.3% of patients in the pemigatinib arm and 15.5% of patients in the chemotherapy arm received 1 cycle of gemcitabine plus cisplatin prior to random assignment. The mean time since diagnosis was 0.6 years (standard deviation [SD], 0.88) in the pemigatinib arm vs 0.6 months (SD, 0.98) in the chemotherapy arm.
Data also showed the ORR with pemigatinib was 47.0% vs 15.5% with gemcitabine plus cisplatin (odds ratio [OR], 5.57; P < .0001), including complete responses in 6.0% vs 3.6% and partial responses in 41.0% vs 11.9% of patients, respectively.
The respective DCRs were 89.2% and 67.9% (OR, 4.10; P = .0007). Median DOR reached 14.2 months (95% CI, 8.7-24.7) with pemigatinib vs 6.3 months (95% CI, 4.3-not estimable) with gemcitabine plus cisplatin (HR, 0.40; 95% CI, 0.16-1.01; P = .0526).
Five patients in the pemigatinib group underwent surgical resection, and all were alive at study closure. Approximately 80% of patients in the chemotherapy group transitioned to FGFR inhibitor therapy, including pemigatinib, after disease progression.
OS was not significantly different between arms, with a median OS of 24.4 months (95% CI, 18.6-35.9) for pemigatinib vs 25.0 months (95% CI, 18.7-34.2) with gemcitabine plus cisplatin (HR, 1.095; 95% CI, 0.733-1.637; P = .6581). Among patients (n = 14) in the chemotherapy group who did not receive FGFR inhibitor therapy after progression, the median OS was 11.1 months.
The safety profile of pemigatinib was consistent with its established profile. All patients in the pemigatinib group (n = 83) and all evaluable patients in the chemotherapy group (n = 73) experienced at least one treatment-emergent adverse effect (TEAE); grade 3 or higher TEAEs occurred in 78.3% vs 67.1% of patients, respectively.
TEAE-related discontinuations were lower with pemigatinib (6.0%) vs gemcitabine plus cisplatin (11.0%). Three fatal TEAEs occurred in the pemigatinib group, which included sepsis, asthenia, and renal failure; however, none were considered related to pemigatinib.
The most common TEAEs in reported in at least 40% of patients treated with pemigatinib comprised hyperphosphatemia (81.9%), alopecia (56.6%), palmar-plantar erythrodysesthesia syndrome (47.0%), stomatitis (45.8%), constipation (44.6%), and diarrhea (44.6%).
An exploratory circulating tumor DNA analysis identified emergent secondary FGFR2 mutations at progression in approximately one-third of patients treated with pemigatinib, including 21 of 63 evaluable patients treated with the agent at any point, 15 of 45 treated in the first line, and 6 of 18 treated after crossover. FGFR2 p.Asn549 (40%) and p.Val564 (23%) variants were most frequently detected.
This article was supported in part by Incyte. Content independently developed and published by OncLive.
