Updated Analysis of the LUC2001 Study

2022 Year in Review: Cholangiocarcinoma — January 4, 2023

The ongoing open-label, multicenter, phase 2a LUC2001 study is investigating the efficacy and safety of the FGFR inhibitor erdafitinib in a molecularly defined subset of Asian patients with advanced cholangiocarcinoma (CCA) harboring FGFR alterations whose disease progressed after ≥1 previous systemic therapies. Updated results from this study were shared at the 2022 ASCO GI Cancers Symposium.

Key inclusion criteria included age ≥18 years, histologically or cytologically confirmed diagnosis of advanced CCA and ≥1 FGFR gene fusions or mutations, ECOG performance status 0-1, and disease progression after ≥1 previous lines of systemic therapy. Eligible patients received erdafitinib 8 mg once daily, with pharmacodynamically guided up-titration to 9 mg once daily. The primary end point was objective response rate (ORR); secondary end points included best overall response, disease control rate, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

Of the 232 patients who had molecular screening, 39 (16.8%) patients had FGFR alterations, including 21 (9.1%) fusions and 19 (8.2%) mutations. Overall, 22 patients were evaluable in this analysis; the median age of this subset was 52 years (range, 29-69 years), the majority (59.1%) were men, 72.7% had malignant intrahepatic CCA, 22.7% had extrahepatic CCA, and 54.5% had received ≥2 previous lines of systemic therapy.

At a median follow-up of 22.4 months (median treatment duration, 6.2 months), the investigator-assessed ORR was 40.9% (9 patients), including 1 complete response and 8 partial responses, with a median time to response of 1.8 months (range, 1.5-5.6 months). The median DOR was 7.3 months (95% confidence interval [CI], 3.7-17.5 months), the median PFS was 5.6 months (95% CI, 3.6-12.7 months), and the median OS was 40.2 months (95% CI, 9.9-not estimable). Overall, 8 of 14 patients with FGFR fusions and 1 of 8 patients with FGFR mutations had a response to treatment with erdafitinib.

All 22 patients had ≥1 treatment-emergent adverse events (TEAEs); the most common TEAEs included dry mouth (68.2%), stomatitis (63.6%), increased alanine aminotransferase (ALT; 50%), increased aspartate aminotransferase (45.5%), and dry skin (45.4%). Grade ≥3 adverse events occurred in 68.2% of patients, of which 50% were TEAEs. The most common grade ≥3 TEAEs were stomatitis (13.6%) and increased ALT (13.6%). Serious TEAEs were reported in 50% of patients. An event of special interest was detachment of retinal pigment epithelium in 1 patient, and 1 patient died of sepsis (which was not treatment-related).

Based on these results, the researchers concluded that erdafitinib therapy was associated with durable efficacy and a manageable safety profile in patients with advanced CCA harboring FGFR alterations.

Source: Feng YH, Su WC, Oh DY, et al. Updated analysis with longer follow up of a phase 2a study evaluating erdafitinib in Asian patients (pts) with advanced cholangiocarcinoma (CCA) and fibroblast growth factor receptor (FGFR) alterations. American Society of Clinical Oncology Gastrointestinal Cancers Symposium 2022. Abstract 430.

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