Immunotherapy/Radiation Shows Responses in NSCLC Brain Metastases

"In the era of immunotherapy, this study presents compelling real-world evidence elucidating the potential benefits of integrating ICIs with [BRT] in the [treatment] of [patients with] NSCLC with [brain metastases], accentuating its favorable impact on OS despite the absence of statistical significance in our findings," according to the study authors.

Combining immune checkpoint inhibitors (ICIs) with brain radiotherapy (BRT) improved the intracranial objective response rate (iORR) without increasing the incidence of serious adverse effects (AEs) among patients with non–small cell lung cancer (NSCLC) and brain metastases, according to findings from a retrospective study published in Scientific Reports.¹

Among 82 evaluable patients for intracranial responses, data showed an iORR of 58.5% (95% CI, 47%-69%) across all patients, 49.1% (95% CI, 35%-63%) among those who received ICIs alone, and 75.9% (95% CI, 56%-90%) in those who were treated with ICIs plus BRT (P = .034). Investigators highlighted some evidence that the addition of BRT to ICIs improved overall survival (OS) vs ICIs alone, although there was no significant difference in outcomes between arms (HR, 0.652; 95% CI, 0.339-1.258; P = .201).

Based on univariate and multivariate analyses, 2 independent prognostic factors included the presence of extracranial metastases (HR, 3.74; 95% CI, 1.28-10.94) and combination chemotherapy (HR, 0.06; 95% CI, 0.01-0.34). Additionally, receipt of corticosteroids or mannitol (Osmitrol) correlated with improved OS in the ICIs plus BRT group vs ICI alone group (HR, 0.16; 95% CI, 0.03-1.01; P = .05). Regarding the remaining patients, investigators noted no statistically significant difference in prognosis across the 2 treatment groups.

“In the era of immunotherapy, this study presents compelling real-world evidence elucidating the potential benefits of integrating ICIs with [BRT] in the [treatment] of [patients with] NSCLC with [brain metastases], accentuating its favorable impact on OS despite the absence of statistical significance in our findings,” Ruoyu Lu, from the Department of Oncology at Xiangya Hospital, Central South University, Changsha, China, wrote with study coauthors.¹

Investigators retrospectively collected data on patients with NSCLC and brain metastases who received first-line ICIs at Xiangya Hospital, Xiangya Changde Hospital, and Xiangya Boai Hospital from 2020 to October 2023. Patients with a diagnosis of NSCLC with brain metastases at initial presentation, at least 1 evaluable brain lesion corroborated by MRI at initial diagnosis, and administration of frontline ICI therapy were eligible for inclusion. Those with small cell lung cancer, a lack of measurable brain metastases identified at initial diagnosis, or prior treatment with other antineoplastic agents before ICIs were ineligible.

Investigators stratified patients into 2 cohorts based on whether they received BRT. Radiotherapy was defined as any BRT modality such as whole-brain radiation and stereotactic radiosurgery.

The study’s primary end points were iORR and ORR. Secondary end points included progression-free survival (PFS), intracranial PFS, OS, and treatment-related toxicity.

Among patients who received immunotherapy alone (n = 99) and those who received immunotherapy in combination with radiation (n = 39), most were male (86.9% vs 89.7%), had prior smoking history (74.7% vs 74.4%), and had no prior drinking history (60.6% vs 66.7%). Additionally, most patients in each respective group had adenocarcinoma (58.6% vs 74.4%), stage T4 disease (45.5% vs 38.5%), stage N3 disease (52.5% vs 56.4%), PD-L1 expression of 1% to 49% (26.3% vs 25.6%), an ECOG performance status of less than 2 (96.0% vs 94.9%), and multiple brain metastases (76.8% vs 84.6%).

Overall, serious AEs leading to discontinuation of ICIs were reported in 6.1% (n = 6) of patients who received ICIs alone. These toxicities included single instances of myelosuppression, elevated amylase, and myocarditis.

In alignment with the 2022 American Society for Radiation Oncology (ASTRO) guidelines, the study authors support the use of ICIs alone for patients with asymptomatic brain metastases while combining ICIs with BRT for those with symptomatic brain metastases.²

“Although data from 3 centers were included, we acknowledge that the patient sample size was limited. Future large-scale prospective trials are warranted to evaluate [BRT] combined with ICIs in the treatment of NSCLC [brain metastases],” the study authors added.¹ “Until further prospective data are available, we believe our findings offer critical insights and actionable guidance for clinicians [treating patients with] NSCLC with [brain metastases].”

References

1. Lu R, Wang Z, Tian W, et al. A retrospective study of radiotherapy combined with immunotherapy for patients with baseline brain metastases from non-small cell lung cancer. Sci Rep. Published online February 27, 2025. doi:10.1038/s41598-025-91863-7
2. Vogelbaum MA, Brown PD, Messersmith H, et al. Treatment for brain metastases: ASCO-SNO-ASTRO guideline. J Clin Oncol. 2022;40(5):492-516. doi:10.1200/JCO.21.02314. Erratum in: J Clin Oncol. 2022;40(12):1392. doi:10.1200/JCO.22.00593