Furmonertinib outperforms gefitinib as first-line therapy in patients with EGFR-mutated NSCLC

In the phase 3 FURLONG study, the third-generation tyrosine kinase inhibitor furmonertinib significantly prolonged progression-free survival (PFS) in patients with treatment-naïve, EGFR-mutated, stage IIIB–IV non-small cell lung cancer (NSCLC), compared with gefitinib.

Furmonertinib is an irreversible, selective, third-generation EGFR tyrosine kinase inhibitor. The phase 3, randomised, double-blind FURLONG study (NCT03787992) aimed to compare the efficacy and safety of furmonertinib versus gefitinib in untreated, advanced NSCLC patients with EGFR-sensitizing mutations.

The trial enrolled 358 patients with treatment-naïve, stage IIIB–IV NSCLC whose tumours were EGFR mutation-positive. Patients were randomised 1:1 to receive furmonertinib 80 mg/day or gefitinib 250 mg/day first-line treatment. In the furmonertinib and gefitinib arms, 35% and 32% had CNS metastases at baseline, respectively. The primary endpoint was PFS. Secondary endpoints included objective response rate (ORR), duration of response, and overall survival (OS). Dr Yuankai Shi (National Cancer Center, China) presented the first results of the FURLONG study [1].

The median follow-up was 21.0 months in each arm, and median duration of exposure was 18.3 months in the furmonertinib arm versus 11.2 months in the gefitinib arm. The median PFS in the furmonertinib arm was significantly longer than in the gefitinib arm (20.8 vs 11.1 months; HR 0.44; P<0.0001). The PFS benefit was consistent across all pre-specified subgroups, including patients with CNS metastases (HR 0.50; P=0.0028). ORR was 89% versus 84%, respectively, in the furmonertinib and gefitinib arm, and median duration of response was 19.7 versus 10.5 months (OR 0.9; P<0.0001), respectively. OS data were not yet mature.

The frequency of grade ≥3 treatment-related adverse events was 11% in the furmonertinib group versus 18% in the gefitinib group. The most frequent treatment-related events in both treatment arms were diarrhoea, rash, and elevated ALT/AST (see Figure).

Figure: Most frequent treatment-related adverse events in FURLONG [1]



Overall, furmonertinib significantly prolonged PFS in patients with treatment-naïve, EGFR-mutated, stage IIIB-IV NSCLC compared with gefitinib. Despite a longer duration of exposure, furmonertinib showed less grade ≥3 treatment-related adverse events compared with gefitinib. Therefore, these results suggest furmonertinib to be a potential first-line therapy in patients with advanced/metastatic NSCLC.

1. Shi Y-K, et al. Furmonertinib versus gefitinib in treatment-naïve EGFR mutated non-small cell lung cancer: A randomized, doubleblind, multi-center, phase III study (FURLONG). Abstract 1O. ELCC 2022 Virtual Meeting, 30 March–02 April.

 

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Posted on 25 May, 202229 February, 2024