Efficacy of immune checkpoint inhibition compared with chemotherapy in combination with radiation therapy in patients with non-small cell lung cancer and brain metastases undergoing neurosurgical resection

This article was originally published here

JAMA Netw Open. 2022 Apr 1;5(4):e229553. doi: 10.1001/jamanetworkopen.2022.9553.


IMPORTANCE: Patients with brain metastases from non-small cell lung cancer (NSCLC) have been routinely excluded from prospective clinical trials that include treatment with immune checkpoint inhibitors (ICI). Clinical data demonstrating the benefits of ICI, particularly after neurosurgical resection of brain metastases, are scarce.

OBJECTIVE: To assess and compare the association of radiation therapy with ICI to conventional therapy involving radiation therapy and chemotherapy regarding overall survival in a cohort of patients with resection of NSCLC brain metastases.

DESIGN, SETTING, AND PARTICIPANTS: This propensity-matched, single-center, 1:1 comparative efficacy study at Germany’s largest neurosurgical clinic included people who underwent craniotomy with resection of brain metastases from January 2010 to December 2021 with a Histologically confirmed NSCLC. Of 1690 patients with lung cancer and brain metastases, 480 were included in the study. The main exclusion criteria were small cell lung cancer, absence of tumor cells by means of histopathological analysis on resection of brain metastases and patients who underwent biopsy without tumor resection. The association of overall survival with radiotherapy and chemotherapy treatment vs radiotherapy and ICI was assessed.

EXPOSURES: Radiotherapy and chemotherapy vs radiotherapy and ICI after craniotomy and microsurgical resection of cerebral metastases.

MAIN OUTCOMES AND MEASURES: Median overall survival.

RESULTS: Of the entire cohort of patients with NSCLC (N = 384), 215 (56%) were male and 169 (44%) were female. The median age (IQR) was 64 (57-72) years. The 2 cohorts of interest included 108 patients (31%) with radiotherapy and chemotherapy and 63 patients (16%) with radiotherapy and ICI after neurosurgical removal of metastases (before matching). The median follow-up time (IQR) for the total cohort was 47.9 (28.2-70.1) months with 89 patients (23%) censored and 295 (77%) dead at the end of follow-up in December 2021 After equalizing covariates using propensity score matching (62 patients per group), patients receiving radiation therapy and chemotherapy after neurosurgery had significantly lower overall survival (11.8 months; 95% CI; 9 .1-15.2) compared to patients receiving radiotherapy and ICI (23.0 months; 95% CI; 20.3-53.8) (P

CONCLUSIONS AND RELEVANCE: Patients with NSCLC brain metastases undergoing neurosurgical resection had longer overall survival when treated with radiotherapy and ICI after neurosurgery compared with those receiving platinum-based chemotherapy and radiotherapy. Radiation therapy and systemic immunotherapy should be regularly evaluated as treatment options for these patients.

PMID:35486401 | DOI:10.1001/jamanetworkopen.2022.9553

Sara H. Byrd