Immunotherapy plus radiotherapy (RT) improves overall survival (OS), compared with chemotherapy plus RT, in patients with non-small cell lung cancer (NSCLC) who have undergone resection of brain metastases, according to research published in JAMA Network Open

Researchers compared immune checkpoint inhibitor (ICI) therapy plus RT to platinum-based chemotherapy plus RT in 384 patients who had undergone craniotomy with resection of brain metastases. The patients had a median age of 64 years (range, 57-72 years), and 56% were men. 

Of 171 evaluable patients, 108 received chemotherapy plus RT, and 63 received ICIs plus RT. In the chemotherapy group, 53 patients received carboplatin plus another agent (etoposide, gemcitabine, pemetrexed, or paclitaxel), 52 received cisplatin plus another agent (etoposide, gemcitabine, or pemetrexed), and 3 patients received single-agent chemotherapy. 

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Of the 63 patients receiving an ICI, 37 received pembrolizumab alone, 7 received atezolizumab alone, 6 received nivolumab alone, and 13 received pembrolizumab plus carboplatin and pemetrexed. 

For the entire cohort, the median follow-up was 47.9 months, and the cumulated median OS was 10.1 months. 

To account for bias and heterogeneity between the 2 cohorts, the researchers performed a 1:1 propensity score-matching analysis with 62 patients in each group. In this analysis, OS was significantly longer in the ICI group than in the chemotherapy group — 23.0 months and 11.8 months, respectively (P <.001). 

On multivariate analysis, there was a significant reduction in the risk of death with ICIs plus RT (hazard ratio [HR], 0.34; 95% CI, 0.21-0.55; P <.001). 

The analysis also showed a significantly lower risk of death among patients who had undergone primary tumor resection (HR, 0.39; 95% CI, 0.20-0.74; P =.004) and a higher risk of death among patients with extracranial metastases (HR, 1.92; 95% CI, 1.16-3.17; P =.01). 

“These findings suggest that patients with resected NSCLC brain metastases may benefit from subsequent treatment with immune checkpoint inhibitors,” the researchers wrote. “Radiation and systemic immunotherapy should be regularly evaluated as a treatment option for these patients.”

Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Wasilewski D, Radke J, Xu R, et al. Effectiveness of immune checkpoint inhibition vs chemotherapy in combination with radiation therapy among patients with non-small cell lung cancer and brain metastasis undergoing neurosurgical resection. JAMA Netw Open. 2022;5(4):e229553. doi:10.1001/jamanetworkopen.2022.9553