P3.04-22 Response of Brain Metastases in Patients with Non-Small Cell Lung Cancer Treated with Immunotherapy and Brain Directed Radiotherapy

Abstract

Background: Immune checkpoint inhibitors (ICIs) targeting PD-(L)1 have shifted the treatment paradigm of advanced non-small cell lung cancer (NSCLC), but responses are often heterogeneous and temporary. Several landmark publications have confirmed the dominant role of gut microbiome in modulating tumor responses to ICIs, suggesting the predictive value of antibiotics (ATB) in patients treated with anti-PD-(L)1 antibody. However, more evidence is needed to comprehensively reveal the association between ATB usage and ICIs therapeutic response in NSCLC, especially in Chinese populations. Method: We retrospectively reviewed the medical records of patients with advanced/metastatic NSCLC received anti-PD-(L)1 based therapies at our hospital. Detailed clinicopathologic characteristics, response data and ATB usage were collected for all patients. The patients receiving ATB within one month around the first administration of ICIs (defined as ATB-treated) were compared to those without (ATB-untreated). Result: 109 cases receiving anti-PD-(L)1 based therapies and underwent response evaluation were identified. 65 (59.3%) of them received monotherapy and 44 received combination therapies including anti-PD-(L)1 plus anti-angiogenesis/chemotherapy. 35 (32.1%) patients had been prescribed ATB 60 days before or during the course of ICIs treatment, and 20 (18.3%) were categorized as ATB-treated group. The most commonly administered ATB were b-lactam inhibitors, fluoroquinolones and macrolides. No major statistical differences in baseline clinicopathologic features were observed between ATB-treated and -untreated groups. The objective response rates (ORR) to ICIs in two groups were 65% and 82%, respectively. ATB treatment was significantly associated with shorter progression-free survival (PFS) (median 3.73 vs 9.3 m, p<0.001), and also tended to be associated with primary disease progression (35% vs 18%, p¼0.087). The overall survival (OS) (median 31.9 vs 37.6 m, p¼0.74) was similar in two groups, but ATB appeared to be related to decreased duration of survival from ICI treatment start to death (median 6.07 vs 26.9 m, p¼0.002). In multivariable analysis, ATB treatment was markedly associated with poorer ORR and survival to ICIs after adjusting for prior line treatment setting, ICI regimens, numbers of ICI-related toxicity and clinical characteristics. Conclusion: ATB usage was a predictor for decreased clinical benefit from anti-PD-(L)1immunotherapies in Chinese NSCLC patients. More comprehensive understanding of the interaction between gut microbiome and ATB is still in urgent need. Furthermore, modulating ATB-related gut microbiome dysbiosis may enhance response to anti-PD-(L)1 immunotherapies.Background: The phase III trials of nivolumab, pembrolizumab or atezolizumab in comparison to standard chemotherapy for advanced non-small cell lung cancer (NSCLC) included a small number of patients with brain metastases. The aim of this study was to evaluate the radiological features of brain metastases after treatment with radiotherapy (...

Radiotherapy combined with PD‐1/PD‐L1 inhibitors in NSCLC brain metastases treatment: The mechanisms, advances, opportunities, and challenges

“…To improve the prognosis and overcome resistance, some clinical studies have also suggested that PD‐1 and PD‐L1 inhibitors combined with radiotherapy (RT) may be expected to improve the anti‐cancer efficacy. 3 , 4 , 5 Preclinical studies have shown that RT can regulate the immune system, including inducing the abscopal effect, increasing the infiltration and activity of tumor‐related lymphocytes, and elevating the number of tumor neoantigens. 6 The combination of PD‐1/PD‐L1 inhibitors with WBRT/SRS should be evaluated in the era of immunotherapy (IO).…”