Survival of melanoma patients treated with targeted therapy and immunotherapy after systematic upfront control of brain metastases by radiosurgery

Combination of Immunotherapy and Brain Radiotherapy in Metastatic Melanoma: A Retrospective Analysis

“…At the end, the wide time span of the cases enrolled (from 2012 to 2016) led to lack of homogeneity between the available treatments, which is not completely in line with current practice (e.g., high prevalence of ipilimumab and WBRT over anti-PD1 agents and SBRT, respectively). This could be of particular concern considering the most recent data showing a favorable outcome with the combination of anti-PD1 and SBRT, but quite worse results with anti-CTLA4 [22-24]. With all these limitations, the present study seems to evidence an absence of synergy between brain RT and ICIs in MM.…”

“…The result was more unsatisfactory with anti-CTLA4 (median OS 7.5 months). Gaudy-Marqueste et al [24] evaluated a cohort of patients with MM treated with targeted drugs, anti-PD1 agents, or chemotherapy in concomitance with SBRT, finding a particularly strong synergy with the combination of anti-PD1 and RT (median OS 14.8 months). As prospective data are lacking, the issue of identifying any synergy between RT and systemic treatments for MM remains unsolved.…”

Radiotherapy as a Backbone for Novel Concepts in Cancer Immunotherapy

“…A retrospective analysis of patients treated for brain metastases of malignant melanoma revealed that inhibition of the PD-1 axis was more effective than inhibition of CTLA-4 in combination with external beam radiotherapy and that concurrent dosing (at least 4 weeks within the two treatments) was necessary to induce best responses [163]. Independent retrospective studies and one meta-analysis confirmed these results [145,[164][165][166][167][168][169][170][171] (Table 4), also showing the superiority of combining radiation with PD-1 inhibitors compared to combination with other agents such as v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) or dual specificity mitogen-activated protein kinase kinase (MEK) inhibitors [172,173] (Table 4). One retrospective study showed longer overall survival of patients irradiated more than 16 weeks after initiation of ipilimumab, compared to patients irradiated within 16 weeks of starting ipilimumab treatment [174].…”

“…Mouse experiments have shown that external beam irradiation more potently synergized with a combination of CTLA-4 and PD-1 blockade than with the respective single agents [137]. In a retrospective clinical analysis, a small (n = 4) group of patients treated with this combination exhibited higher one-year overall survival than groups treated with radiation and respective single agents [173]. A mouse study has shown the merit of blocking other immune checkpoints in combination with PD-1 axis blockade and radiation in order to maximize effectiveness [209].…”

“…26 patients received radiation (r), 28 received radiation and anti-CTLA-4 (c), 11 received radiation and anti-PD-1 (p), and 39 received radiation and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) and dual specificity mitogen-activated protein kinase kinase (MEK) inhibitors (b) median overall survival was 11 months (r), 8 months (c), 20 months (p), and 18 months (b)Gaudy-Marqueste et al 2017[173] N melanoma brain metastases BRAF-mutated patients were treated with radiation (mr) (n = 29) or radiation combined with BRAF and/or MEK inhibitors alone (mm) (n = 34), combined with anti-CTLA-4 or anti-PD-1 (mc), or anti-CTLA-4 or anti-PD-1 alone (mi); BRAF wildtype patients were treated with radiation alone (r) or combined with anti-CTLA-4 (c) anti-PD-1 (p) or both (b)…”