Anti-PD1 Therapy Plus Whole-Brain Radiation Therapy May Prolong PFS in Selected Non–Small Cell Lung Cancer Patients with Brain Metastases: A Retrospective Study

Muhammad Khan,1,2 Zhihong Zhao,3 Xianming Li,1 Guixiang Liao1 1Department of Oncology, Shenzhen People’s Hospital, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, People’s Republic of China; 2Department of Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 3Department of Nephrology, Shenzhen People’s Hospital, Second Clinical Medicine Centre, Jinan University, Shenzhen, People’s Republic of ChinaCorrespondence: Guixiang Liao; Xianming LiDepartment of Radiation Oncology, Shenzhen People’s Hospital, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, People’s Republic of ChinaEmail liaoguixiang@163.com; chenlhnfy@163.comBackground: Whole-brain radiotherapy (WBRT) remains an essential modality of treatment for brain metastases (BMs) derived from non-small cell lung cancer (NSCLC) patients and anti-PD-1 therapy has demonstrated intracranial responses in these patients. We aimed to evaluate if the combination of the two treatments could yield additive efficacy.Methods: A retrospective review of our institution’s database was carried out to identify NSCLC patients with BMs who had been treated with anti-PD1 therapy and/or WBRT between 2015 and 2020. Patient characteristics, main outcomes, including progression-free survival (PFS) and overall survival (OS), and factors affecting these outcomes were analyzed. SPSS 24 was used for statistical analysis. Appropriate statistical tests were employed according to the type of data.Results: Overall, 21 NSCLC BM patients were identified that had received WBRT. Of these, ten had been additionally treated with anti-PD1 therapy within 30 days of WBRT initiation. Median PFS was 3 (95% CI 0.8– 5.1) months with WBRT alone versus 11 (95% CI 6.3– 15.6) months with combined treatment. Risk of disease progression was 71% lower with the combined approach (HR 0.29, 95% CI 0.11– 0.80; p=0.016). A trend toward improved OS was also observed with the combined approach (HR 0.33, 95% CI 0.08– 1.12; p=0.107). Concurrent treatment (p=0.028) and male sex (p=0.052) were associated with improved PFS, while OS was associated only with age (p=0.02).Conclusion: Concurrent WBRT and anti-PD1 therapy may delay progression and improve survival in BM patients with confirmed EGFR- and ALK-negative NSCLC histology. Prospective studies are warranted to validate and elucidate on the additive effect of the two modalities.Keywords: brain metastasis, BM, whole-brain radiation therapy, WBRT, non–small cell lung cancer, NSCLC, immune checkpoint blockade, ICB, combination, combined therap