Correlation of Clinical Parameters with Intracranial Outcome in Non-Small Cell Lung Cancer Patients with Brain Metastases Treated with Pd-1/Pd-L1 Inhibitors as Monotherapy

Abstract

There is a paucity of biomarkers for the prediction of intracranial (IC) outcome in immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients (pts) with brain metastases (BM). We identified 280 NSCLC pts treated with ICIs at Karolinska University Hospital, Sweden, and University Hospital of Heraklion, Greece. The inclusion criteria for response assessment were brain metastases (BM) prior to ICI administration, radiological evaluation with CT or MRI for IC response assessment, PD-1/PD-L1 inhibitors as monotherapy, and no local central nervous system (CNS) treatment modalities for ≥3 months before ICI initiation. In the IC response analysis, 33 pts were included. Non-primary (BM not present at diagnosis) BM, odds ratio (OR): 13.33 (95% CI: 1.424–124.880, p = 0.023); no previous brain radiation therapy (RT), OR: 5.49 (95% CI: 1.210–25.000, p = 0.027); and age ≥70 years, OR: 6.19 (95% CI: 1.27–30.170, p = 0.024) were associated with increased probability of IC disease progression. Two prognostic groups (immunotherapy (I-O) CNS score) were created based on the abovementioned parameters. The I-O CNS poor prognostic group B exhibited a higher probability for IC disease progression, OR: 27.50 (95% CI: 2.88–262.34, p = 0.004). Age, CNS radiotherapy before the start of ICI treatment, and primary brain metastatic disease can potentially affect the IC outcome of NSCLC pts with BM.

Prognostic Factors and Survival Benefits of Antitumor Treatments for Advanced Non-Small Cell Lung Cancer Patients With Central Nervous System Metastasis With or Without Driver Genes: A Chinese Single-Center Cohort Study

“…The combination of ICI with radiotherapy for BM has a good safety tolerance, and both local control rate and overall survival of patients are improved, compared with radiotherapy alone ( 29 ). Longer progression-free survival was also achieved with the addition of radiotherapy to ICIs ( 30 , 31 ). Due to the research period of this study, immunotherapy has not been widely used in the Chinese population, and only a few patients were included.…”

Brain metastases, patterns of intracranial progression, and the clinical value of upfront cranial radiotherapy in patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors

“…To date, numerous studies have been published focusing on the impact and timing of cranial RT in relation to anti- PD-1/PD-L1 therapy for metastatic NSCLC (8,(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

Clinical determinants impacting overall survival of patients with operable brain metastases from non-small cell lung cancer

“…A recent study by Rounis etal. ( 19 ) focused specifically on a subgroup of patients who received PD-1/PD-L1 inhibitors as treatment for NSCLC BM and found that specific clinical parameters, such as age <70 years, prior CNS radiation, and the synchronous appearance of BM, significantly affected ICB disease control. However, it is important to point out that this study was focused on the patients who received ICB as monotherapy, as opposed to the patients included in our cohort, who received any combination of CT and ICB.…”