Two phase 2 studies of futibatinib, a highly selective irreversible fibroblast growth factor receptor (FGFR)1-4 inhibitor, analyzed data from the FOENIX-CCA2 clinical trial and were presented at the 2020 virtual meeting of the European Society for Medical Oncology (ESMO).
FOENIX-CCA2 is an ongoing, global, open-label phase 2 clinical trial that enrolled patients with locally advanced or metastatic unresectable intrahepatic cholangiocarcinoma (CCA) and FGFR2 fusions or rearrangements. Approximately 10% to 20% of patients with CCA have FGFR2 fusions.
Of the 103 patients participating in FOENIX-CCA2, 67 patients were included in each of the 2 studies presented at ESMO. The first study analyzed efficacy and safety data, and the second study evaluated quality-of-life (QOL) outcomes. In 2018, the FDA granted futibatinib an orphan drug status.
In the first study, John A. Bridgewater, PhD, FRCP, Professor of Medical Oncology, Department of Medical Oncology, University College London Cancer Institute, England, and colleagues presented data from the FOENIX-CCA2 clinical trial for 67 patients who received futibatinib and had a minimum of 6-month follow-up. Most (82%) of these patients had FGFR2 fusions.
The primary end point of the study was the objective response rate (ORR), as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 criteria, which was confirmed by a second tumor assessment 4 to 6 weeks after the initial response. The secondary end points included the duration of response, disease control rate, progression-free survival, and safety.
The ORR with futibatinib was 37.3%, with a median duration of response of 8.3 months; and 37% of the patients are still receiving treatment. The subgroup analysis revealed that patients aged ≥65 years had a better ORR than younger patients under age 65 years (57.1% vs 32.1%, respectively), and female patients had a better ORR than male patients (43.6% vs 28.6%, respectively).
The adverse events reported were consistent with those seen in other FGFR inhibitors. Of note, patients who responded to treatment with futibatinib had higher phosphate levels than nonresponders. This is noteworthy, because the most common adverse event in the patients who received futibatinib was hyperphosphatemia.
A phase 3 clinical trial of futibatinib versus gemcitabine and cisplatin for the first-line treatment of patients with intrahepatic CCA and FGFR2 rearrangements is underway.
The second study examined the health-related QOL data from the FOENIX-CCA2 clinical trial. This is the first report of QOL data for an FGFR inhibitor in patients with intrahepatic CCA. Juan W. Valle, MB ChB, MSc, FRCP, Division of Cancer Sciences, University of Manchester, England, and colleagues collected patient-reported outcomes (PROs) from the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EuroQol-5D (EQ-5D-3L) QOL instruments.
The EORTC QLQ-C30 is composed of 5 multi-item scales (ie, physical, role, social, emotional, and cognitive functioning) and 9 single items (ie, pain, fatigue, financial impact, appetite loss, nausea/vomiting, diarrhea, constipation, sleep disturbance, and QOL). The EQ-5D-3L is a QOL measure with 1 question for each of 5 dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
A total of 67 patients were included in the interim analysis, of whom 57 (85%) patients had PROs available. The investigators collected PROs at screening, then at cycles 2 and 4, then every 3 cycles, and at the end of treatment. The mean QLQ-C30 score was sustained and was stable in terms of individual function and symptom measures from baseline through treatment cycle 13 (ie, 273 days) of futibatinib.
The only clinically meaningful increase in QLQ-C30 score (ie, an increase of ≥10 points) was a worsening of constipation at cycles 2 and 4 (+12.4 and +10.7 points, respectively). The mean EQ-5D-3L score demonstrated an increasing trend from baseline to cycle 13, which suggests that patients had improved QOL and health.
Overall, the PROs from the FOENIX-CCA2 are encouraging, the investigators concluded, noting that treatment with futibatinib does not adversely affect patients’ QOL.
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