First-Line Tyrosine Kinase Inhibitors Combined With Local Consolidative Radiation Therapy for Elderly Patients With Oligometastatic Non-Small Cell Lung Cancer Harboring EGFR Activating Mutations

Abstract

ObjectiveThe aim of this study was to investigate the efficacy and safety of combined applications of local consolidative radiation therapy (LCRT) and first-line tyrosine kinase inhibitors (TKIs) for the treatment of primary tumors and oligometastatic sites in oligometastatic NSCLC harboring Epidermal Growth Factor Receptor (EGFR) activating mutations.Patients and MethodsElderly patients with oligometastatic NSCLC (≤5 metastases) harboring EGFR activating mutations at the time of diagnosis were identified. They were treated with first-line TKIs alone or in combination with LCRT. Progression‐free survival (PFS) and overall survival (OS) were estimated through the Kaplan–Meier method.ResultsA total of 122 elderly patients were enrolled between February 2010 and January 2018. Among them, 41.0% (n = 50) received TKIs combined with LCRT (TKIs + LCRT group), whereas 59.0% (n = 72) received TKIs monotherapy (TKIs alone group). Patients were followed up for a median length of 34 months (ranging from 7.0 to 64 months). The median PFS in TKIs + LCRT group was 17 months (95%CI: 15.37–18.63), which was significantly longer than that of the TKIs-alone group (12 months; 95%CI: 11.05–12.95) (p <0.001). Median OS in TKIs + LCRT group was 38 months (95%CI: 35.61–40.39), while that of the TKIs-alone group was 29 months (95%CI: 26.86–31.14) (p <0.001). Multivariate analyses revealed that LCRT, one to two metastases, and good ECOG PS were independent predictors for better PFS (p <0.001, p = 0.004, and p = 0.027). Moreover, LCRT, good ECOG PS, and T1-2 stage were independent predictors for better OS (p <0.001, p = 0.007 and p = 0.007). Most of the patients suffered from grade 1 to 2 toxicities, and treatment-related deaths were not recorded.ConclusionFirst-line TKIs combined with LCRT may improve survival outcomes for elderly patients with oligometastatic NSCLC harboring EGFR activating mutations. This approach was not associated with much toxicity, therefore, it can be used for the treatment of elderly patients with oligometastatic disease.

Post-progression survival in advanced non-small cell lung cancer treated with anti-PD-1/PDL-1 monotherapy: progression after durable clinical benefit versus primary resistance

“…Such a strategy has been shown as potentially beneficial in oncogene-addicted aNSCLC, but results of comparative prospective studies remain to be published. 29 In spite of these theoretical advantages, a minority of PD after DCB (4/43 – 9.3%) was treated with local therapies in our cohort (Supplementary Table S3). This might be due, to some extent, to the lack of follow-up data available at that time for clinician to support such treatments in PD after DCB.…”

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

“…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 OS range in the LT group was 25.5 months to not reached, whereas in the TKI group, it was 17.6 to 60.0 months ( 36 , 37 , 39 , 40 , 43 - 46 ).…”

“…Funnel plot analyses were conducted to evaluate the potential reporting bias. The HRs of median PFS from all 11 studies were included, and HRs of median OS from the eight studies were also included in the funnel plot analyses ( Figure S2 ) ( 36 , 37 , 39 , 40 , 43 - 46 ). The funnel plots were symmetric, and Egger’s test values for them were 0.71 and 0.34, respectively, which indicated no apparent reporting bias.…”

“…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 ).…”

Image‐guided thermal ablation for patients with epidermal growth factor receptor‐mutant nonsmall cell lung cancer

“…In the abovementioned study, regarding the complications of postablation, moderate pain was observed in 27 patients (38.0%), pneumothorax occurred in 23 patients, seven patients required chest tube drainage, nine patients had pleural effusion, of whom one required chest tube drainage, and 20 patients had postablation syndrome. There have also been several trials addressing the importance of IGTA in patients with NSCLC with oligoprogression 45–52 (See Table 1 for details). In fact, some studies have reported the relative mechanisms explaining why local ablation could prolong the PFS and OS of patients with oligoprogressive NSCLC with resistance to EGFR‐TKIs, and researchers have believed that local ablation could influence the EGFR/PI3K/AKT pathway, but a large sample size is needed to explore the detailed mechanism 53 …”