What question did this study set out to answer?

This study aimed to assess first-line treatment effectiveness for patients with PACC-mutant NSCLC.

April 22, 2026Open Access

A real-world study on the comparative effectiveness of first-line treatment regimens in advanced NSCLC patients with PACC mutations

Puntos clave

This study aimed to assess first-line treatment effectiveness for patients with PACC-mutant NSCLC.
Conducted a retrospective cohort study involving 100 patients diagnosed with PACC-mutant NSCLC between 2015 and 2025.
Evaluated the efficacy of various first-line treatment regimens, specifically comparing chemotherapies and TKIs.
Utilized IPTW-weighted analyses to support findings.
TKIs significantly improved progression-free survival (PFS) compared to chemotherapy (14.2 vs 5.2 months, HR = 0.348, p = 0.005).
Third-generation TKIs showed promising outcomes for patients with brain metastases, leading to longer PFS and overall survival compared to second-generation TKIs.
Subgroup analyses revealed longer PFS for S768I mutations compared to E709X under TKI treatment.

Resumen

Background: P-loop and αC-helix compressing ( PACC ) mutations are a distinct structural subset of atypical epidermal growth factor receptor ( EGFR ) alterations in non-small-cell lung cancer (NSCLC), yet no standard first-line strategy has been established. Objectives: This study aimed to evaluate first-line treatment outcomes in patients with PACC -mutant NSCLC. Design: A real-world retrospective study. Methods: This retrospective cohort study enrolled 100 patients with PACC -mutant NSCLC who were diagnosed between February 2015 and April 2025. The efficacy of different first-line treatment strategies in this population was evaluated. Results: Among the 100 patients, compared with chemotherapy, treatment with tyrosine kinase inhibitors (TKIs) significantly prolonged progression-free survival (PFS; 14.2 vs 5.2 months, hazard ratio (HR) = 0.348, p = 0.005). The inverse probability of treatment weighting (IPTW)-weighted Cox analysis produced results consistent with the primary analysis (IPTW-adjusted HR = 0.487, p = 0.039). Among patients treated with TKIs, both second-generation (13.9 vs 13.1 months, HR = 0.338, p = 0.015) and third-generation TKIs (16.8 vs 13.9 months, HR = 0.239, p = 0.011) appeared to be associated with longer PFS compared with first-generation TKIs; however, given the relatively small subgroup sizes, these comparisons should be interpreted with caution. In patients with brain metastases, third-generation TKIs were associated with numerically longer PFS (28.0 vs 11.2 months, HR = 0.324, p = 0.132) and significantly longer overall survival (not reached vs 29.0 months, HR = 0.097, p = 0.030) compared with second-generation TKIs. In patients with a single PACC mutation, second-generation TKIs significantly prolonged PFS compared with non-second-generation TKIs (18.0 vs 11.0 months, HR = 0.347, p = 0.032). In addition, subgroup analyses indicated that, relative to the E709X subset, patients with S768I mutations had significantly prolonged PFS under TKI treatment (24.6 vs 10.6 months, HR = 0.263, p = 0.027). Conclusion: TKIs may represent a promising first-line option for advanced NSCLC with PACC mutations. The choice of specific TKIs may depend on genomic characteristics and brain metastasis status.

Leer artículo completoexternamente

Me gusta

Guardar

Ver artículo completo