BRIGHTSTAR Final Analysis evaluates the efficacy of local consolidation therapy brigatinib in patients with TKI-naïve, ALK-rearranged non-small cell lung cancer

In a recent final analysis of BRIGHTSTAR, researchers delved into the efficacy of Brigatinib alone as a treatment for tyrosine kinase (TKI)-naïve, ALK-regulated metastatic non-small cell lung cancer (NSCLC) compared with brigatinib combined with local consolidation therapy (LCT), and said the latter showed "promising results." This discovery provides new ideas and directions for the treatment of patients with metastatic NSCLC.

The importance of this study is that existing data show that 95% of ALK TKI-initiated patients do not achieve complete remission after treatment, showing the presence of residual disease, which not only affects the patient's quality of life, but also increases the possibility of acquired resistance. Therefore, the researchers propose that combating these residual diseases with LCT may be able to delay the progression of drug resistance and improve patient clinical outcomes. This idea provides a more comprehensive treatment strategy for the management of ALKTKI-naïve patients.

The study adopted a single-center trial design and recruited 34 TKI-naïve ALK-rearranged metastatic NSCLC patients, covering different types of oligometastatic and multi-metastatic disease. Participants first received an 8-week induction therapy with brigatinib, followed by local consolidation therapy, including radiotherapy and/or surgery, based on the patient's specific conditions. Among all patients, 32 (94%) received further LCT after initial treatment with brigatinib, demonstrating the feasibility and acceptability of this treatment regimen in patient management.

The research team performed "comprehensive annotation" of the patients' tumor images at baseline and at different time points after brigatinib induction, using an "overall 3D tumor volume" approach to define disease burden. This quantitative approach allows for a clearer assessment of tumor development and response to treatment. In addition, the researchers retrospectively compared the final analysis results of this study with data from other phase III trials to further verify the validity and reliability of the study.

When describing the patient's disease status at baseline, the study results showed that,Twenty-eight patients (82%) experienced multiple metastases at the start of the study, of which 14 (41%) had brain metastases. This feature makes patient treatment more complex and also reflects the diverse treatment needs of patients with metastatic NSCLC. In local consolidation therapy (LCT), various methods such as radiotherapy, surgery, and surgery combined with radiotherapy are used. Adverse events of grade 3 or higher in the study include esophagitis, pneumonia, anemia, adrenal insufficiency, and bronchopulmonary hemorrhage, etc., prompting clinicians to carefully evaluate potential risks during treatment.

The results of the study showed that the median progression-free survival (PFS) reached 66 months, and the 5-year PFS was 51%. By comparison, in previous trials evaluating brigatinib monotherapy, patients had a median PFS of 29.4 months. This significant prolongation of survival highlights the importance of LCT in treatment options. Among patients who were positive for circulating tumor DNA (ctDNA) at baseline (n = 16), PFS was 28 months, while those who were ctDNA negative (n = 13) did not reach median PFS, further supporting the potential of ctDNA as an important biomarker for monitoring treatment response.

In addition, the study also found that patients with a total tumor volume exceeding 55 cm³ at baseline had a median progression-free survival of 27.5 months, while patients with a total tumor volume less than 55 cm³ did not reach the median progression-free survival, showing a close association between tumor volume and prognosis. Based on the final analysis results, the researchers divided the patients into high-risk and low-risk groups. Patients in the high-risk group had significantly worse PFS, with a risk ratio of 11.6 (95% CI, 2.51-53.8), which provides an important basis for clinical decision-making.

Overall, the researchers concluded that patients receiving comprehensive local consolidation therapy (LCT) have favorable outcomes and that baseline ctDNA status and tumor volume measurements serve as valid prognostic biomarkers. This discovery not only provides a new perspective for the treatment of metastatic NSCLC, but also provides a solid theoretical basis for future clinical trial design and patient management. With the deepening of research, it is believed that more significant progress will be made in the field of combating metastatic non-small cell lung cancer.

References:https://www.cancernursingtoday.com/post/brightstar-final-analysis-evaluates-local-consolidative-therapy-plus-brigatinib-for-patients-with-tki-naive-alk-rearranged-nsclc