Abstract
BackgroundIn pivotal immunotherapy trials, the efficacy of immune checkpoint inhibitors as treatments for lung cancer patients with brain metastases remains controversial. The aim of this study was to assess the relative efficacy of immunotherapy versus standard systemic therapy in advanced lung cancer patients with and without brain metastases.MethodsSystematic searches of PubMed, Embase, Cochrane database, and conference proceedings up to Aug 6, 2020 without year and language restrictions. The main outcomes were the overall survival in patients with and without brain metastases measured by hazard ratios, and the difference in efficacy between patients with and without brain metastases was measured by ratio of hazard ratios.ResultsNine eligible randomized controlled trials involving 6241 patients (682 [11%] with brain metastases and 5559 [89%] without brain metastases) were included in the analysis. A survival benefit of immunotherapy was observed for both patients with brain metastases (HR, 0.75; 95%CI, 0.53-0.97; P = .026) and patients without brain metastases (HR, 0.75; 95%CI, 0.67-0.83; P <.001). However, patients without brain metastases benefit more from immunotherapy than patients with brain metastases (HR, 1.37; 95%CI, 1.15-1.63; P = .001). Additionally, subgroup analyses indicated that tumor type affect the efficacy of immunotherapy in patients with brain metastases (HR, 1.04 vs 1.54; interaction, P = .041).ConclusionsImmunotherapy can significantly improve overall survival for advanced lung cancer patients with asymptomatic brain metastases, especially in patients with non-small-cell lung cancer, but the magnitude of benefit is brain metastases dependent.Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020206597.
Highlights
IntroductionThe efficacy of immune checkpoint inhibitors as treatments for lung cancer patients with brain metastases remains controversial
In pivotal immunotherapy trials, the efficacy of immune checkpoint inhibitors as treatments for lung cancer patients with brain metastases remains controversial
The main outcomes were the overall survival in patients with and without brain metastases measured by hazard ratios, and the difference in efficacy between patients with and without brain metastases was measured by ratio of hazard ratios
Summary
The efficacy of immune checkpoint inhibitors as treatments for lung cancer patients with brain metastases remains controversial. The aim of this study was to assess the relative efficacy of immunotherapy versus standard systemic therapy in advanced lung cancer patients with and without brain metastases. With the emergence of novel systemic treatments and the development of diagnostic imaging technology, survival time of cancer patients extended which increasing the chance of developing brain metastases, and the detection rate of brain metastases has increased [1]. The main treatments available for patients with a limited number of brain metastases are surgery and stereotactic radiotherapy [4]. Whole-brain radiotherapy is the standard of care for patients with symptomatic multiple brain metastases [5]. The management of multiple asymptomatic brain metastases usually adopts systemic therapy [6]. Systemic therapy for patients without sensitizing mutations are still lacking
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