Patient-reported outcomes for the phase 3 FURLONG study of furmonertinib versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer

Abstract

Background: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) in the FURLONG study. Here we present prespecified secondary endpoints of patient-reported outcomes (PRO).

Methods: In this multicentre, double-blind, double-dummy, randomised phase 3 study, patients were 1:1 randomly assigned to receive furmonertinib 80 mg once daily or gefitinib 250 mg once daily. PROs assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 and Quality-of-Life Questionnaire Lung Cancer 13 were analysed using a mixed model for repeated measures and time-to-event analyses. A difference in score of 10 points or more was deemed clinically relevant.

Findings: Three hundred and fifty-seven patients (furmonertinib group, n = 178; gefitinib group, n = 179) received at least one dose of the study drug, all of whom completed at least one PRO assessment. Statistically significant difference of overall score changes from baseline favoured furmonertinib in physical functioning (between-group difference 2.14 [95% CI 0.25-4.04], p = 0.027), nausea/vomiting (-1.56 [95% CI -2.62 to -0.49], p = 0.004), appetite loss (-2.24 [95% CI -4.26 to -0.23], p = 0.029), diarrhoea (-3.36 [95% CI -5.19 to -1.54], p < 0.001), alopecia (-2.62 [95% CI -4.54 to -0.71], p = 0.007), and pain in other parts (-4.55 [95% CI -7.37 to -1.74], p = 0.002), but not reached clinical relevance. Time to deterioration in physical functioning (hazard ratio 0.63 [95% CI 0.42-0.94], p = 0.021), cognitive functioning (0.73 [95% CI 0.54-0.98], p = 0.034), nausea/vomiting (0.64 [95% CI 0.41-0.99], p = 0.042), appetite loss (0.63 [95% CI 0.43-0.92], p = 0.016), diarrhoea (0.63 [95% CI 0.46-0.85], p = 0.002), dyspnoea (0.72 [95% CI 0.53-0.98], p = 0.034), cough (0.67 [95% CI 0.44-1.00], p = 0.049), dysphagia (0.54 [95% CI 0.35-0.83], p = 0.004), and alopecia (0.62 [95% CI 0.42-0.90], p = 0.012) was longer with furmonertinib versus gefitinib.

Interpretation: In patients with locally advanced or metastatic EGFR mutation-positive NSCLC, furmonertinib showed improved scores and delayed deterioration in several functioning and symptoms compared to gefitinib.

Funding: Shanghai Allist Pharmaceutical Technology Co., Ltd and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

Keywords: AST2818; Epidermal growth factor receptor; Furmonertinib; Non-small cell lung cancer; Patient-reported outcomes.

Fig. 1

Study profile. ∗Ten patients had two reasons for screening failure.

Fig. 2

Changes in HRQoL, cough, and chest pain from baseline to week 90. For HRQoL, higher scores denote improved functioning; for symptom scales, higher scores denote worse symptoms. Data are mean change in mixed model for repeated measures-adjusted scores, error bars indicate 95% CI around the mean. Data were (A) HRQoL, (B) cough and (C) chest pain based on relevant items in the QLQ-LC13 and QLQ-C30. HRQoL, health-related quality of life; CI, confidence interval; QLQ-C30, European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30; QLQ-LC13, European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Lung cancer 13.

Fig. 3

Time to deterioration of HRQoL, functioning, symptoms, and financial difficulty. Data are time to deterioration based on relevant items in the QLQ-LC13 and QLQ-C30, hazard ratios and 95% CI were calculated by use of the COX proportional hazards model, p values were calculated with a stratified log-rank test. HRQoL, health-related quality of life; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30; HR, hazard ratio; CI, confidence interval; EORTC QLQ-LC13, European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Lung Cancer 13.