Survival and prognostic factors of HER2-mutant advanced non-small cell lung cancer with brain metastases.

BACKGROUND

Brain metastases (BM) represent a common complication in non-small-cell lung cancer (NSCLC) with human epidermal growth factor receptor 2 (HER2) mutations. We aimed to characterize the BM incidence and its association with genetic subtypes, and to analyze treatment outcomes and prognostic factors in this patient population.

METHODS

Between July 2018 and July 2023, we retrospectively screened 6536 patients with advanced NSCLC. A total of 183 patients with HER2-mutant NSCLC were identified, of whom 91 had BM. The primary study endpoint was overall survival (OS).

RESULTS

The median follow-up period was 18.1 months (range 5.0-39.7) at the cut-off date of December 28, 2023. Incidence of BM at diagnosis was 24.6 % (45/183), and overall BM incidence was 49.7 % (91/183). There was no significant difference in the lifetime incidence of BM between the HER2 exon20 YVMA insertion and non-YVMA insertion subtypes (p = 0.558). The median OS of 91 patients with BM was significantly lower than that of patients without BM (14.8 vs. 23.2 months, p < 0.001). All patients with BM received chemotherapy-based treatments as first-line treatment. For second or later-line treatment, 28 patients (30.8 %) received antibody-drug conjugates (ADCs) and 17 patients (18.7 %) tyrosine kinase inhibitors (TKIs). Patients who had received ADC treatments demonstrated superior OS compared to those who had received TKI treatments or those who only received chemotherapy-based treatments (18.4 vs. 13.2 vs. 13.8 months, p = 0.008). Additionally, brain radiotherapy was significantly associated with improved survival outcomes (16.9 vs. 12.3 months, p = 0.001). Multivariate analysis identified that ADC treatments, brain radiotherapy, ECOG PS scores, and BM-related symptoms were independent prognostic factors (p < 0.05 for all).

CONCLUSION

The BM incidence in HER2-mutated NSCLC is high and similar across genetic subtypes. ADC treatments may potentially contribute to prolonged OS for patients with HER2-mutated NSCLC and BM. Besides, brain radiotherapy could confer significant OS benefits.