Multiple resistant factors in lung cancer with primary resistance to EGFR-TK inhibitors confer poor survival

Kim, Go Woon; Song, Joon Seon; Choi, Chang‐Min; Rho, Jin Kyung; Kim, Sun Ye; Jang, Se Jin; Park, Young Soo; Chun, Sung-Min; Kim, Woo Sung; Lee, Jung Shin; Lee, Dong Hoon; Lee, Jae Cheol

doi:10.1016/j.lungcan.2015.01.023

Cited by 30 publications

(26 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10 studies were eventually identified and the corresponding authors were contacted. We received individual patient data for 7 of these studies [22, 25–28, 30, 37]. Authors of 3 studies did not reply ( n = 502) [24, 29, 31].…”

Section: Resultsmentioning

confidence: 99%

A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundA germline deletion in the BIM (BCL2L11) gene has been shown to impair the apoptotic response to tyrosine kinase inhibitors (TKIs) in vitro but its association with poor outcomes in TKI-treated non-small cell lung cancer (NSCLC) patients remains unclear. We conducted a systematic review and meta-analysis on both aggregate and individual patient data to address this issue.ResultsIn an aggregate data meta-analysis (n = 1429), the BIM deletion was associated with inferior PFS (HR = 1.51, 95%CI = 1.06–2.13, P = 0.02). Using individual patient data (n = 1200), we found a significant interaction between the deletion and ethnicity. Amongst non-Koreans, the deletion was an independent predictor of shorter PFS (Chinese: HR = 1.607, 95%CI = 1.251–2.065, P = 0.0002; Japanese: HR = 2.636, 95%CI = 1.603–4.335, P = 0.0001), and OS (HR = 1.457, 95% CI = 1.063–1.997, P = 0.019). In Kaplan-Meier analyses, the BIM deletion was associated with shorter survival in non-Koreans (PFS: 8.0 months v 11.1 months, P < 0.0005; OS: 25.7 v 30.0 months, P = 0.042). In Koreans, the BIM deletion was not predictive of PFS or OS.Materials and Methods10 published and 3 unpublished studies that reported survival outcomes in NSCLC patients stratified according to BIM deletion were identified from PubMed and Embase. Summary risk estimates were calculated from aggregate patient data using a random-effects model. For individual patient data, Kaplan-Meier analyses were supported by multivariate Cox regression to estimate hazard ratios (HRs) for PFS and OS.ConclusionsIn selected populations, the BIM deletion is a significant predictor of shorter PFS and OS on EGFR-TKIs. Further studies to determine its effect on response to other BIM-dependent therapeutic agents are needed, so that alternative treatment strategies may be devised.

show abstract

Section: Resultsmentioning

confidence: 99%

A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Primary resistance is another challenge in clinical practice, however, the mechanism is not well investigated currently. Coexistent genetic alterations in cancer-driving genes, i.e., KRAS mutations, PTEN loss and BIM polymorphisms were identified to be associated with primary resistance for EGFR-TKIs treatment [13–14]. But, most studies focused on concurrent ALK and EGFR mutations [15–16].…”

Section: Introductionmentioning

confidence: 99%

Concurrent gene alterations with EGFR mutation and treatment efficacy of EGFR-TKIs in Chinese patients with non-small cell lung cancer

Liu

Chen

2017

Oncotarget

View full text Add to dashboard Cite

PurposeWe investigated the frequency of concurrent genes in EGFR-mutant non-small cell lung cancer patients and determined its value in predicting the efficacy of EGFR-TKIs treatment.MethodsThree hundred and twenty patients, who harbored EGFR activating mutations and received EGFR-TKIs treatment, were examined for another eight genes including KRAS, NRAS, PIK3CA, BRAF, and HER2 mutations and ALK, ROS1, and RET fusion genes based on reverse transcription PCR. Progression-free survival and overall survival with EGFR-TKIs treatment were evaluated using Kaplan-Meier methods and compared between different patients using log-rank tests.RESULTSTwenty-one (6.6%) of 320 EGFR mutant samples with additional gene alterations were identified. The most common concurrent gene was PIK3CA mutation (n = 9), followed by EML4-ALK rearrangement (n = 6), HER2 mutation (n = 3), RET rearrangement (n = 1), ROS1 rearrangement (n = 1) and KRAS mutation (n = 1). Patients with single EGFR mutation had a significantly longer progression-free survival than those with concurrent genes (10.9 vs. 6.0 months, P = 0.002). Among the 21 cases, patients with PIK3CA mutation had the longest median progression-free survival (7.6 months), followed by ALK rearrangement (5.0 months) and other gene types (1.2 months). No overall survival difference was found between patients with single EGFR mutation and concurrent gene alterations (21.0 vs.17.6 months, P = 0.17).ConclusionWe demonstrated that concurrent gene alterations occurred in some patients with EGFR mutations. Concurrent gene alterations decreased the efficacy of EGFR-TKIs.

show abstract

“…Possible contributing factors included T790M mutation, MET amplification and PIK3CA mutation 7–9. Concomitant genetic alterations were found to be associated with primary resistance in EGFR -mutated NSCLC patients 10,11. However, the studies were somewhat limited, and only several case series were reported.…”

Section: Introductionmentioning

confidence: 99%

ALK and ROS1 concurrent with EGFR mutation in patients with lung adenocarcinoma

Mao

2017

OTT

View full text Add to dashboard Cite

PurposeThe purpose of this study was to explore the frequencies of ALK and ROS1 fusion genes in EGFR-mutant lung adenocarcinoma patients and examine the therapeutic efficacies of EGFR-tyrosine kinase inhibitors (TKIs).Materials and methodsA total of 421 EGFR-mutated patients taking EGFR-TKIs were examined for ALK and ROS1 fusion genes based on reverse transcription-polymerase chain reaction (RT-PCR). Progression-free survival (PFS) and overall survival (OS) were evaluated by the Kaplan–Meier method and compared by the log-rank test.ResultsThe mutations of ALK rearrangement (n=10) and ROS1 rearrangement (n=3) were detected. All the patients received EGFR-TKIs, and eight took subsequent ALK/ROS1 inhibitor. PFS was longer in single EGFR mutants (n=408) than in EGFR/ALK or EGFR/ROS1 counterparts (n=13; 10.7 vs 6.6 months, P=0.004). No difference in OS existed between single EGFR and EGFR/ALK or EGFR/ROS1 mutants (21.0 vs 23.0 months, P=0.196). The median PFS of eight patients treated with ALK/ROS1 inhibitor was 6.0 months.ConclusionConcomitant ALK/ROS1 fusion genes occurred in 3.1% EGFR-mutated lung adenocarcinoma patients. Concomitant ALK/ROS1–EGFR mutations may influence the therapeutic efficacy of EGFR-TKIs.

show abstract

Multiple resistant factors in lung cancer with primary resistance to EGFR-TK inhibitors confer poor survival

Cited by 30 publications

References 50 publications

A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer

A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer

Concurrent gene alterations with EGFR mutation and treatment efficacy of EGFR-TKIs in Chinese patients with non-small cell lung cancer

<em>ALK</em> and <em>ROS1</em> concurrent with <em>EGFR</em> mutation in patients with lung adenocarcinoma

Contact Info

Product

Resources

About