Thoracic stereotactic body radiation therapy plus first-line tyrosine kinase inhibitors for patients with epidermal growth factor receptor-mutant polymetastatic non-small-cell lung cancer

Abstract

The role of thoracic stereotactic body radiation therapy (SBRT) in addition to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant polymetastatic non-small-cell lung cancer (NSCLC) has not been well established. This retrospective study aimed to evaluate the efficacy and safety of EGFR-TKIs with thoracic SBRT for the treatment of this patient group. Polymetastatic NSCLC was defined as having >5 metastatic lesions. Patients with polymetastatic NSCLC harboring positive EGFR mutations after initial TKI therapy for at least 8 weeks were eligible for SBRT between August 2016and August 2019. Eligible patients were treated with thoracic SBRT, and TKIs were administered for the duration of SBRT and continued after SBRT until they were considered ineffective. The control group was treated with TKI monotherapy. Propensity score matching (ratio of 1:4) was used to account for differences in baseline characteristics. Progression-free survival (PFS), overall survival, and treatment safety were evaluated. In total, 136 patients were included in the study population. Among them, 120 patients received TKIs alone, and 16 patients received TKIs with thoracic SBRT. The baseline characteristics did not significantly differ between the two cohorts after propensity score matching. The median PFS was 17.8 months in the thoracic SBRT group and 10.8 months in the control group ( P = .033). In the multivariate analysis, a Cox regression model showed that thoracic SBRT was an independent statistically significant positive predictor of improved survival, with a hazard ratio of 0.54 ( P = .046). We recorded no severe toxic effects or grade 4 to 5 toxicities. Real-world data demonstrate that thoracic SBRT significantly extends PFS in EGFR-mutant polymetastatic NSCLC patients with tolerable toxicity. Given these results, randomized studies are warranted.

Pre-radiotherapy systemic immune inflammation index associated with overall survival in patients with advanced EGFR mutant non-small cell lung cancer receiving thoracic radiotherapy

“…A study showed that curative radiotherapy for primary lung lesion can prolong survival in patients with lung adenocarcinoma following EGFR-TKI treatment, involving both patients with oligometastasis and polymetastasis [ 5 ]. Some clinical studies have shown that EGFR TKIs combined with thoracic radiotherapy for advanced NSCLCs with EGFR mutation provides long-term control of primary lung tumors [ 6 – 8 ]. Our previous study also confirmed that thoracic radiotherapy was associated with prolonged median OS for this subpopulation patients [ 9 ].…”

Additional local therapy before disease progression for EGFR-mutated advanced lung cancer: a systematic review and meta-analysis

“…Among the 11 studies, the HRs of median OS were reported in eight studies ( 36 , 37 , 39 , 40 , 43 - 46 ). In the remaining three studies, Wang et al reported median OS but did not reach an HR ( 41 ), whereas the other two studies did not report HR data of median OS ( 38 , 42 ). In the eight studies that provided HRs, the pooled HR of median OS between the LT and TKI groups was 0.42 (95% CI: 0.36–0.48; P<0.001), which indicated a significant benefit in favor of the LT group, with a low heterogeneity (P=0.19; I 2 =30%) ( Figure 2B ).…”

“…The median ‘time to LT’ ranged from 0 to 6.6 months. Five studies were classified into the early LT group ( 36 , 39 , 41 , 43 , 46 ), and the other six were classified into the late LT group ( 37 , 38 , 40 , 42 , 44 , 45 ). The pooled HRs of median PFS in the early and late LT groups were 0.35 (95% CI: 0.26–0.47) and 0.33 (95% CI: 0.26–0.42), respectively (P=0.710) ( Figure 3A ).…”

“…Based on the number of metastatic foci, six studies included patients with OM ( 36 , 38 , 39 , 43 , 45 , 46 ), two studies included patients with PM ( 41 , 42 ), and three studies included patients without any restriction on the number of metastatic foci ( 37 , 40 , 44 ). Among the OM group, five studies defined OM as five or fewer metastatic lesions ( 36 , 39 , 43 , 45 , 46 ), whereas Chan et al defined OM as four or fewer metastatic lesions ( 38 ).…”

Survival benefit of thoracic radiotherapy plus EGFR-TKIs in patients with non-oligometastatic advanced non-small-cell lung cancer: a single-center retrospective study

“… 15 , 30 , 31 Moreover, several studies have examined the activity of thoracic radiation in advanced NSCLC patients harboring TKI-sensitive EGFR mutations. 22 , 23 , 32 , 33 Zheng et al conducted a prospective study to assess the efficacy of thoracic radiotherapy in combination with EGFR-TKIs on stage IV EGFR mutant lung adenocarcinomas. 22 A superior 1-year PFS was observed in the combination therapy group.…”