medwireNews: Individuals with non-small-cell lung cancer (NSCLC) and brain metastases may benefit from treatment with immune checkpoint inhibitors (ICIs) plus radiotherapy after neurosurgical resection, findings indicate.
“Although patients undergoing surgical brain metastasis removal are regularly treated with different systemic therapies, prospective randomized clinical studies are lacking for this patient cohort,” explain the researchers in JAMA Network Open.
And they add: “Retrospective data may help in further evaluating the role of local and systemic treatment modalities specifically in cohorts of surgically treated patients.”
The team therefore identified 171 NSCLC patients aged a median of 62 years who received radiotherapy (local, whole-brain, or stereotactic radiosurgery) plus at least two cycles of either ICIs (n=63) or platinum-based chemotherapy (n=108) after undergoing resection of brain metastases at one of the three sites of the Charité University Medical Hospital in Germany during 2010–2021.
Nearly two-thirds (59%) of the ICI-treated patients received pembrolizumab monotherapy, 11% received atezolizumab monotherapy, and 10% nivolumab monotherapy, while the remaining 20% received pembrolizumab plus chemotherapy.
A propensity score-matched analysis, with 62 patients in each group, showed significantly longer overall survival (OS) among those who received ICIs rather than chemotherapy alongside radiation, at a median of 23.0 versus 11.8 months.
This finding “was corroborated by means of multivariable Cox regression analysis,” which showed a significant 66% reduced risk for death with receipt of ICIs versus chemotherapy after adjusting for confounders such as the number of brain metastases, report David Wasilewski (Charité – Universitätsmedizin Berlin) and co-investigators.
Other factors that were significantly associated with OS in this analysis were receipt of primary tumor resection (hazard ratio [HR]=0.39) and the presence of extracranial metastases (HR=1.92).
The team speculates that “[t]he possible benefit of surgery with adjuvant radiation therapy and ICIs is likely based on biologic effects mediated by radiation-induced cancer cell damage with subsequent release of tumor antigens and blockade of immunosuppressive signaling.”
Wasilewski and colleagues highlight some limitations of the study, including the lack of data on “cause of death, intracranial and extracranial progression-free survival, and extent of brain metastasis resection because of incomplete follow-up documentation,” as well as the absence of information on “important biomarkers” such as PD-L1 status.
They continue: “Although propensity score matching is an adequate statistical solution for balancing covariates of treatment and control groups, the relatively small sample size with only 63 patients in the ICI group is also a limiting factor of the study.”
Nevertheless, the team believes that the findings indicate “a potential benefit with ICI use in this patient cohort and highlight the importance of combinatory and interdisciplinary treatment approaches in patients with brain metastasis.”
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JAMA Netw Open 2022; 5: e229553