e20669 Background: Although ALK inhibitors significantly improve the prognosis of ALK fusion-positive non-small cell lung cancer (NSCLC) patients, different ALK fusion detection methods may be used in clinical practice. Reverse-transcription polymerase chain reaction (RT-PCR) detects known, predefined fusion sites, while next-generation sequencing (NGS) can identify other rare or unknown fusion subtypes. Both methods are widely used in China. This study aims to explore the differences in efficacy of ALK inhibitors in patients identified by RT-PCR versus NGS and to investigate the impact of ALK fusion patterns and molecular characteristics on prognosis. Methods: We retrospectively analyzed 153 patients with advanced ALK -positive NSCLC who received first-line targeted therapy, identified by RT-PCR (n = 71) or NGS (n = 82). Inverse probability of treatment weighting (IPTW) was applied, incorporating covariates such as clinical characteristics and treatment drugs. Cox models were used to compare progression-free survival (PFS) and overall survival (OS) between the two groups. In the NGS group, fusion patterns were defined as: classic fusion (containing only EML4-ALK fusion), non-classic fusion (containing no EML4-ALK fusion), and complex fusion (containing both types). Cox regression models were used to evaluate the prognostic factors. Risk factors for early treatment failure (PFS < 12 months) were analyzed. Statistical tests were two-sided, with P < 0.05 considered significant. Results: The median PFS of patients in the NGS group was significantly shorter than that in the RT-PCR group (19.0 vs. 48.0 months; HR, 2.73; P < 0.001), and their OS was also worse (NR vs. NR; HR, 2.18; P = 0.035). Univariate analysis showed that patients in the non-classic fusion group (n = 13) had worse median PFS compared to the classic fusion group (n = 34) (13.0 vs. 23.1 months; HR, 2.14; P = 0.038). However, multivariate analysis confirmed that only TP53 mutation was an independent risk factor for PFS (HR, 4.36; P < 0.001) and OS (HR, 6.14; P = 0.005). Additionally, TP53 mutation (OR, 4.50; P = 0.023), co-existing other gene mutations (OR, 3.00; P = 0.044), and non-V1/V2/V3 EML4-ALK fusion variants (OR, 7.50; P = 0.023) were potential risk factors for early treatment failure. Conclusions: This study suggests that ALK -positive patients identified by NGS may differ in treatment response and prognosis from those identified by RT-PCR, with significantly worse PFS and OS. ALK fusion patterns themselves are not strong independent prognostic factors. TP53 mutations, other co-existing mutations, and rare non-V1/V2/V3 EML4-ALK fusion variants are noteworthy risk markers that may guide intensified monitoring and treatment strategies for high-risk patients. Further research is needed to confirm these findings.
Xie et al. (Thu,) studied this question.