Furmonertinib emerges as potential first-line option for EGFRm NSCLC

Treatment-naïve patients with locally advanced or metastatic EGFR-mutated (EGFRm) non-small-cell lung cancer (NSCLC) experience improved progression-free survival (PFS) when treated with furmonertinib compared with gefitinib, according to results of the phase III FURLONG study.

The multicentre, double-blind trial, conducted in 55 centres in China, involved 358 adults with treatment-naïve locally advanced or metastatic EGFRm NSCLC and ECOG performance status (PS) 0–1. They were randomized 1:1 to receive furmonertinib (80 mg QD) or gefitinib (250 mg QD) until disease progression, unacceptable toxicity, new therapy initiation, or consent withdrawal.

The median age of patients in the furmonertinib and gefitinib groups was 59 and 60 years, respectively, and 65 and 62 percent, respectively, were female. ECOG PS was 1 in 76 and 84 percent, respectively, and 0 in 22 and 16 percent, respectively. Thirty-five and 32 percent, respectively, had central nervous system (CNS) metastases, and 77 and 75 percent did not have a history of smoking. Almost all patients had stage IV disease. Fifty-one percent of each group had Ex19del mutations and 49 percent each L858R mutations.

At data cut-off after 62 percent maturity, PFS was significantly improved among patients in the furmonertinib than gefitinib group (median 20.8 vs 11.1 months; hazard ratio [HR], 0.44, 95 percent confidence interval [CI], 0.34–0.58; p<0.0001). [ELCC 2022, abstract 10]

The results were consistent across subgroups including age, sex, ECOG PS, smoking history, CNS metastases, and type of EGFR mutation.

Objective response rate did not significantly differ between the furmonertinib and gefitinib groups (89 percent vs 84 percent; odds ratio [OR], 1.50, 95 percent CI, 0.80–2.83; p=0.2078), nor did disease control rate (96 percent vs 93 percent; OR, 1.56, 95 percent CI, 0.61–3.98; p=0.3551) or depth of response (median 61.1 percent vs 55.9 percent; p=0.0852).

In contrast, duration of response was significantly longer with furmonertinib than gefitinib (median 19.7 vs 10.5 months; OR, 0.39, 95 percent CI, 0.29–0.52; p<0.0001), as was time to progression (median 20.9 vs 11.2 months; OR, 0.41, 95 percent CI, 0.31–0.55; p<0.0001).

Overall survival was not reached in either group (HR, 0.94; p=0.7446). Forty-three percent of patients in the gefitinib group received third-generation EGFR-TKIs* following progression.

Patients in the furmonertinib and gefitinib groups received treatment for a median 18.3 and 11.2 months, respectively. Grade ≥3 treatment-emergent adverse events (TEAEs) were documented in 35 and 34 percent, respectively, and serious TEAEs in 25 and 16 percent, respectively. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 11 and 18 percent, respectively, and serious TRAEs in 6 percent in each group. TRAEs led to dose interruption in 13 percent vs 16 percent and discontinuation in 3 percent vs 2 percent. Five furmonertinib recipients required dose reduction. No TRAEs led to death in either group.

The most frequent grade 3–4 TRAE in the furmonertinib group was diarrhoea (2 percent), while the most common in the gefitinib group were elevated alanine aminotransferase and aspartate aminotransferase levels (7 and 6 percent, respectively). Nine and seven percent of patients in the furmonertinib and gefitinib groups, respectively, had documented QT prolongation, while one patient in each group had interstitial lung disease (grade 1 in the furmonertinib group and grade 2 in the gefitinib group).

“In this randomized, double-blind, phase III FURLONG study, furmonertinib was associated with a significantly longer PFS compared with gefitinib in untreated EGFR-mutated NSCLC. This benefit is consistent across prespecified subgroups,” presented Professor Yuankai Shi from the National Cancer Center and National Clinical Research Center for Cancer and Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, at ELCC 2022.

“Despite a longer duration of exposure, furmonertinib showed an overall favourable safety profile vs gefitinib, with relatively lower frequency of grade ≥3 TRAEs.”

“These results suggest that furmonertinib is a potential preferred first-line therapy in EGFRm Chinese NSCLC patients compared with gefitinib,” Shi concluded.