Concurrent Immune Checkpoint Inhibitors and Stereotactic Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma
Menée à partir de données portant sur 260 patients traités entre 2010 et 2016 pour une ou plusieurs métastases cérébrales ayant pour origine un cancer du poumon non à petites cellules, un mélanome ou un carcinome à cellules rénales, cette étude évalue l'intérêt, du point de vue de la survie sans progression, de la survie globale et du taux d'événements indésirables, d'un traitement combinant de manière concomitante radiochirurgie stéréotaxique et inhibiteurs de point de contrôle immunitaire
Purpose : To characterize the effect of concurrent stereotactic radiosurgery/stereotactic radiotherapy (SRS/SRT) and immune checkpoint inhibitors (ICI) on patient outcome and safety in patients with brain metastases (BM). Materials/Methods : We retrospectively identified metastatic non-small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma (RCC) patients who had BM treated with SRS/SRT from 2010-2016 without prior whole brain radiotherapy (WBRT). We included SRS/SRT patients who were treated with anti-CTLA4 (ipilimumab) and anti-PD-1 (nivolumab, pembrolizumab). Patients who were given ICI on active or unreported clinical trials were excluded, and concurrent ICI was defined as given within 2 weeks of SRS/SRT. Patients were managed with SRS/SRT, SRS/SRT with non-concurrent ICI, and SRS/SRT with concurrent ICI. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier survival curves, and cox proportional hazard models were used for multivariate analysis. Logistic regression was used to identify predictors of acute neurologic toxicity, immune-related adverse events (irAEs), and new BM. Results : 260 patients were treated with SRS/SRT to 623 brain metastases. 181 were treated with SRS/SRT only and 79 with SRS/SRT and ICI, with 35% of patients treated with concurrent SRS/SRT and ICI. Concurrent ICI was not associated with increased rates of irAEs or acute neurologic toxicity and predicted for a decreased likelihood of developing ≥ 3 new BM following SRS/SRT (p=0.045, OR 0.337). Median OS for patients treated with SRS/SRT, SRS/SRT and non-concurrent ICI, and SRS/SRT with concurrent ICI was 12.9, 14.5, and 24.7 months respectively. Concurrent SRS/SRT and ICI was associated with improved OS compared to SRS/SRT only (p=0.002, HR 2.69) and compared to non-concurrent SRS/SRT and ICI (p=0.006, HR 2.40) on multivariate analyses. The OS benefit of Concurrent SRS/SRT and ICI was significant in comparison to patients treated with SRS/SRT pre (p=0.002, HR 3.82) or post (p=0.021, HR 2.64) ICI. Conclusion : Delivering SRS/SRT with concurrent ICI may be associated with decreased incidence of new BM and favorable survival outcomes without increased rates of adverse events.
http://www.redjournal.org/article/S0360-3016(17)34167-6/fulltext 2017