Impact of epidermal growth factor receptor sensitizing mutations on outcomes of patients with non-small cell lung cancer treated with definitive thoracic radiation therapy: a systematic review and meta-analysis

Soon, Yu Yang; Vellayappan, Balamurugan; Tey, Jeremy; Leong, Cheng Nang; Koh, Winston T. H.; Tham, Ivan

doi:10.18632/oncotarget.21019

Cited by 5 publications

(4 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, this expected difference has not been observed in the results obtained in clinical trials. In a systematic review to explore the impact of EGFR-sensitizing mutations on the outcomes of patients with NSCLC treated with definitive TRT, [64] Soon et al identified 7 studies that included 537 patients with stage III NSCLC. Up to 45% of the patients in these studies had mutations in exon 19 and 21.…”

Section: Discussionmentioning

confidence: 99%

Epidermal growth factor receptor tyrosine kinase inhibitors combined with thoracic radiotherapy or chemoradiotherapy for advanced or metastatic non-small cell lung cancer: A systematic review and meta-analysis of single-arm trials

et al. 2019

View full text Add to dashboard Cite

Background: Preclinical in vitro experiments demonstrated that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) might have synergistic effect in combination with radiotherapy on Non-small cell lung cancer (NSCLC), but the clinical trials showed inconsistence results in NSCLC patients with EGFR status unknow or mutations. This study aimed to determine if added TKIs to Thoracic radiotherapy (TRT) improve primary disease response rate (RR) and survival outcomes in advanced or metastatic NSCLC. Methods: We searched MEDLINE, EMBASE, and Cochrane Library from January 2000 to December 2017 for eligible studies where patients received concurrent EGFR TKIs and TRT or CRT. Concerned outcomes were primary tumor RR, overall survival (OS), and adverse events (AEs). The meta-analysis was performed using Stata software (version 12.0). Random effects models were used to pool outcomes across studies. Sensitivity analysis was performed to determine if the results would be different. Results: We found 16 prospective clinical trials with mature results for meta-analyses. Twelve studies including 446 patients reported the RR and survival outcomes of TRT combined TKIs. The CR, PR, SD, and PD, respectively, were 0.06 (95% CI 0.03–0.09, I 2 = 0%), 0.44 (95% CI 0.38–0.49, I 2 = 64.9%), 0.29 (95% CI 0.24–0.34, I 2 = 78.4%), and 0.15 (95% CI 0.11–0.19, I 2 = 84.2%). One- and 2-year OS, respectively, were 0.52 (95% CI 0.44–0.60, I 2 = 38.8%) and 0.26 (95% CI 0.18–0.33, I 2 = 0%). Four studies including 182 patients reported the RR and survival outcomes of CRT combined TKIs. The pooled CR, PR, SD, and PD, respectively, were 0.12 (95% CI 0.02–0.22, I 2 = 69.1%), 0.41 (95% CI 0.27–0.55, I 2 = 71.6%), 0.31 (95% CI 0.16–0.46, I 2 = 79%), and 0.14 (95% CI −0.01–0.30, I 2 = 87.8%). Only 1 study reported the survival event rate, 1- and 2-year OS, respectively, were 0.83 (95% CI 0.71–0.94) and 0.67 (95% CI 0.54–0.81). There were not severe adverse events (SAEs) reported either TRT combined TKIs or CRT combined TKIs. Conclusion: There is evidence, albeit of low quality, that added the TKIs to TRT or CRT may improve RR and survival outcomes in patients with EGFR mutant status unknown advanced or metastatic NSCLC relative to other studies of TKIs alone, TRT alone or CRT.

show abstract

Section: Discussionmentioning

confidence: 99%

Epidermal growth factor receptor tyrosine kinase inhibitors combined with thoracic radiotherapy or chemoradiotherapy for advanced or metastatic non-small cell lung cancer: A systematic review and meta-analysis of single-arm trials

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Epidermal growth factor, a cell surface receptor, regulates cell proliferation, apoptosis, angiogenesis, adhesion, and motility through intracellular signaling and controls tumor progression [8]. Sensitizing EGFR mutations are the most common actionable driver mutations that may induce Tyrosine Kinase (TK) activation and phosphorylation of downstream pathways, resulting in aggravating cancer [9] [10]. In-frame deletions in exon 19 and point mutations in exon 21 (L858R) are the most common EGFR mutations [8].…”

Section: Introductionmentioning

confidence: 99%

Epidemiology of EGFR Mutation in Adenocarcinoma NSCLC Patients in India: A Systematic Review and Meta-Analysis

Jain,

Prabhash,

Radhakrishnan

et al. 2024

ALC

View full text Add to dashboard Cite

Studies reporting the Indian prevalence of Epidermal Growth Factor Receptor (EGFR) mutation are mostly single centers with small sample sizes. This systematic review and meta-analysis summarized the available evidence of EGFR mutation epidemiology in Indian patients with adenocarcinoma (ADC) Non-Small Cell Lung Cancer (NSCLC). We conducted a structured literature search in PubMed, and EMBASE databases from January 2004 through October 2019. The primary outcome of interest was prevalence of EGFR mutation by gender, smoking status, and mutation subtype. The review included 34 studies. EGFR mutation prevalence was 39.5% in patients with ADC, and significantly higher in females, non-smokers, and patients with exon 19 deletions. The EGFR mutation frequency in Indian patients with ADC was higher than reported in Caucasians but at a lower range of that reported in East Asians. These findings support the use of EGFR mutation testing to guide choice of treatment.

show abstract

“… 5 , 6 , 7 , 8 , 9 , 10 , 11 In several studies, patients with EGFR‐mutant LA‐NSCLC were found to have shorter progression‐free survival (PFS) than those without EGFR mutations, 5 , 6 , 7 whereas another study showed that patients with LA‐NSCLC with EGFR‐sensitizing mutations had a trend toward improvement in the overall response rate (ORR) compared with patients without EGFR mutations, with no significant differences in relapse‐free survival (RFS) and overall survival (OS). 12 Most patients with inoperable stage III NSCLC would face loco‐regional and/or distant recurrences in the first 2 years following definitive CRT, 2 , 13 , 14 , 15 with the feasibility and clinical value of salvage local therapy remaining controversial. Metastasectomy or cranial radiation may provide clinical benefit for patients with isolated brain metastases (BMs) following definitive CRT, 16 , 17 whereas re‐irradiations are occasionally performed for patients with loco‐regional recurrence.…”

Section: Introductionmentioning

confidence: 99%

“…Considerable differences in treatment response and pattern of failure may exist between definitive CRT‐treated patients with LA‐NSCLC with or without driver mutations 5–11 . In several studies, patients with EGFR‐mutant LA‐NSCLC were found to have shorter progression‐free survival (PFS) than those without EGFR mutations, 5–7 whereas another study showed that patients with LA‐NSCLC with EGFR‐sensitizing mutations had a trend toward improvement in the overall response rate (ORR) compared with patients without EGFR mutations, with no significant differences in relapse‐free survival (RFS) and overall survival (OS) 12 . Most patients with inoperable stage III NSCLC would face loco‐regional and/or distant recurrences in the first 2 years following definitive CRT, 2,13–15 with the feasibility and clinical value of salvage local therapy remaining controversial.…”

Section: Introductionmentioning

confidence: 99%

Pattern of failure and clinical value of local therapy for oligo‐recurrence in locally advanced non‐small cell lung cancer after definitive chemoradiation: Impact of driver mutation status

Zhang

Mao

et al. 2022

Cancer Medicine

View full text Add to dashboard Cite

Introduction Considerable differences of treatment response and pattern of failure may exist between definitive chemoradiation (CRT) treated locally advanced non‐small cell lung cancer (LA‐NSCLC) patients. The clinical value of additional tyrosine kinase inhibitors (TKIs) before disease recurrence and salvage local therapy after initial recurrent disease remain controversial. Methods and Materials Consecutive LA‐NSCLC patients receiving definitive CRT and having definite results about driver mutations (EGFR, ALK and ROS1) were retrospectively reviewed. Initial recurrent disease was classified as in‐field recurrence, out‐of‐field recurrence and distant metastasis. Recurrent disease occurred only in the brain or limited to ≤3 extra‐cranial organs and ≤5 extra‐cranial lesions, was defined as oligo‐recurrence. Progression free survival and overall survival (OS) were calculated from diagnosis to disease progression or death, and to death, respectively. OS2 was measured from initial disease recurrence to death among patients who had recurrent disease. Results Of the 153 enrolled patients, 39 had driver mutations and 13 received additional TKI therapy besides definitive CRT. Patients harboring driver mutations but without additional TKI therapy had a similar PFS and significantly longer OS ( p = 0.032) than those without driver mutations. Additional TKI therapy prolonged PFS ( p = 0.021) but not OS among patients with driver mutations. No significant difference of pattern of failure was observed between patient subgroups stratified by the status of driver mutations and the usage of additional TKI therapy. Furthermore, 57 of the 95 patients with initial recurrent disease developed oligo‐recurrence and salvage local therapy significantly improved OS2 ( p = 0.01) among patients with oligo‐recurrence disease. Conclusion LA‐NSCLC patients receiving definitive CRT generally had similar PFS and pattern of treatment failure, regardless of driver mutation status. Additional TKI therapy besides definitive CRT could prolong PFS but not OS. The majority of recurrent disease after definitive CRT belongs to oligo‐recurrence and salvage local therapy may provide survival benefit.

show abstract

Impact of epidermal growth factor receptor sensitizing mutations on outcomes of patients with non-small cell lung cancer treated with definitive thoracic radiation therapy: a systematic review and meta-analysis

Cited by 5 publications

References 24 publications

Epidermal growth factor receptor tyrosine kinase inhibitors combined with thoracic radiotherapy or chemoradiotherapy for advanced or metastatic non-small cell lung cancer: A systematic review and meta-analysis of single-arm trials

Epidermal growth factor receptor tyrosine kinase inhibitors combined with thoracic radiotherapy or chemoradiotherapy for advanced or metastatic non-small cell lung cancer: A systematic review and meta-analysis of single-arm trials

Epidemiology of EGFR Mutation in Adenocarcinoma NSCLC Patients in India: A Systematic Review and Meta-Analysis

Pattern of failure and clinical value of local therapy for oligo‐recurrence in locally advanced non‐small cell lung cancer after definitive chemoradiation: Impact of driver mutation status

Contact Info

Product

Resources

About