Growth Factor Receptor T790M Mutation Research Articles

Characterization of the Epidermal Growth Factor Receptor T790M Mutation in Colorectal Cancer.

Characterization of the Epidermal Growth Factor Receptor T790M Mutation in Colorectal Cancer.

Epidermal growth factor receptor T790M mutations in non-small cell lung cancer (NSCLC) of Yunnan in southwestern China

To explore the effect of epidermal growth factor receptor (EGFR) T790M mutation status on non-small cell lung cancer (NSCLC) in Yunnan province of southwestern China. First, this study used the super amplification refractory mutation system (Super ARMS) polymerase chain reaction (PCR) and Droplet Digital PCR (dd PCR) to evaluate the T790M gene mutation, in plasmatic ctDNA samples from 212 cases of NSCLC. The association between T790M mutations and clinical parameters were further explored. Next, to investigate the mechanism of drug resistance that resulted from T790M mutation, subgroup analyses according to duration of medicine (EGFR-TKIs) were carried out. Finally, we also evaluate the effectiveness of blood-based circulating tumor DNA (ctDNA) on detecting the T790M mutation by calculating Super ARMS’s detection efficiency. We found that the T790M mutation rate was 8.4% (18/212) in overall patients. The T790M mutation was more frequent in patients with brain metastasis 30.0% (12/40) (p < 0.01). We found that post-TKI samples 42.8% (15/35) were associated with a higher T790M mutation rate (p < 0.01). Subgroup analysis showed that the duration of TKI therapy for 6 to 10 months 66.6% (8/12) (p < 0.01) and >10 months 75.0% (9/12) (p < 0.01) were also associated with a higher T790M mutation rate. Super ARMS’s sensitivity, specificity, PPV, NPV, and accuracy were 100.0%, 99.4%, 94.7%, 100.0%, and 99.5% respectively. Generally, the EGFR-T790M mutation was more common in NSCLC patients with brain metastasis and those who received TKI therapy for more than 6 months. Moreover, Super ARMS is a sensitive, efficient, and practical clinic method for dynamically monitoring T790M mutation status and effectively guiding clinic treatment.

Efficacy and Safety Data of Osimertinib in Elderly Patients with NSCLC Who Harbor the EGFR T790M Mutation After Failure of Initial EGFR-TKI Treatment.

The aim of this study was to evaluate the safety and efficacy of osimertinib for elderly patients, since the data remain limited. A total of 77 patients with advanced non-small cell lung cancer (NSCLC) harboring the epidermal growth factor receptor (EGFR) T790M mutation and treated with osimertinib were reviewed. Efficacy and safety indicators, such as EGFR-tyrosine kinase inhibitor (TKI)-related adverse events (AEs) and osimertinib-associated hematotoxicity, were evaluated in elderly patients (elderly group, EG; age, ≥75 years) by comparing them with younger patients (non-EG; aged <75 years). The frequency of AEs associated with osimertinib was compared with the initial EGFR-TKI treatment before osimertinib administration in the same patient cohort. Of the total 77 patients, 18 (23%) were assigned to the EG, whereas 59 (77%) were assigned to the non-EG. There were no significant differences in overall response rate and progression-free survival between the two groups. Regarding the safety of osimertinib, the EG had significantly more grade ≥2 paronychia than the non-EG (16.6% vs. 1.6%, p=0.04). Additionally, the maximum grade of EGFR-TKI-related AEs associated with osimertinib in the EG was significantly lower than that of the initial EGFR-TKI treatment (p=0.03). Osimertinib is a safe and effective treatment option for elderly patients with advanced NSCLC who harbor the EGFR mutation.

EGFR T790M Mutation in TKI-Naïve Clinical Samples: Frequency, Tissue Mosaicism, Predictive Value and Awareness on Artifacts

Background: This study evaluated the distribution of epidermal growth factor receptor (EGFR) T790M mutations in treatment-naïve tumor and normal samples obtained from cancer patients. Methods: We utilized allele-specific PCR (AS-PCR), digital droplet PCR (ddPCR) and next generation sequencing (NGS) to detect EGFR T790M allele in several collections of tumor and normal human tissues. Results: AS-PCR analysis of treatment-naïve tumor samples revealed somatic T790M mutation in 3/394 (1%) non-small cell lung carcinomas (NSCLC) carrying the tyrosine kinase inhibitor (TKI)-sensitizing EGFR mutation, but in none of 334 NSCLC lacking EGFR exon 19 deletions (ex19del) or L858R substitutions and in none of 235 non-lung tumors. Use of highly sensitive and quantitative assays, such as ddPCR and NGS, produced a high number of T790M-specific signals even in presumably T790M-negative DNA specimens. This background noise was evidently higher in degraded DNA isolated from formalin-fixed paraffin-embedded tissues as compared to high molecular weight DNA. A combination of AS-PCR, ddPCR and NGS revealed mosaic EGFR T790M allele in 2/68 (3%) NSCLC treated with the first-generation TKI. Both these tumors produced evident and durable response to gefitinib. Conclusion: Detection of mosaic EGFR T790M mutation in treatment-naïve samples may be compromised by yet unresolved technical issues and may have limited clinical value.

Osimertinib With Ramucirumab in EGFR-mutated, T790M-positive Patients With Progression During EGFR-TKI Therapy: Phase Ib Study

BackgroundEpidermal growth factor receptor (EGFR) T790M mutation is the most frequent mechanism of resistance among patients with progression during EGFR-tyrosine kinase inhibitor (TKI) therapy. A third-generation EGFR-TKI, osimertinib, demonstrated durable efficacy with mild adverse events in a phase III trial and is considered a novel standard regimen. The tolerability of osimertinib monotherapy has allowed for the development of a more efficacious combination regimen. Preclinical and clinical study data have suggested that vascular endothelial growth factor inhibition can enhance EGFR-TKI activity with tolerable toxicity. AimsThe aim of the present single-arm, phase Ib study is to assess the tolerability of osimertinib combined with ramucirumab in patients with EGFR-mutated, T790M+ lung cancer with progression during EGFR-TKI therapy. The primary endpoint is to assess the safety of osimertinib plus ramucirumab at a fixed dose. The secondary endpoints are the overall response rate, progression-free survival, overall survival, and safety. Six patients will be enrolled in the trial.

Clinical significance of repeat rebiopsy in detecting the EGFR T790M secondary mutation in patients with non-small cell lung cancer.

BackgroundOsimertinib is an essential drug to treat non-small-cell lung cancer (NSCLC) harboring the epidermal growth factor receptor (EGFR) T790M mutation, and rebiopsy is necessary to detect this mutation. However, the significance of repeat rebiopsy in NSCLC patients whose first rebiopsy was T790M-negative remains unclear. We used a retrospective cohort to clarify this issue.MethodsWe reviewed the medical records of patients with NSCLC harboring EGFR mutations who underwent EGFR tyrosine kinase inhibitor (TKI) treatment at Okayama University Hospital between January 2015 and January 2017.ResultsOf 102 patients with EGFR-mutant NSCLC, 55 underwent rebiopsy after acquired resistance to prior EGFR TKIs. Pre-existing activating EGFR mutations were found in all 55 rebiopsied samples. Of the 55 samples, 25 were T790M-positive (45%). Among the remaining 30 patients (T790M-negative on the first rebiopsy), 21 underwent additional rebiopsies following interval therapy. Of the 21 patients, 11 were T790M-positive on the second rebiopsy and 1 on the third. We also evaluated the efficacy of osimertinib in patients who needed a repeat rebiopsy to detect the T790M mutation. Osimertinib showed good activity with an objective response rate of 50%.ConclusionsRepeat rebiopsy increases the ability to detect a secondary mutation (T790M) in EGFR.

Feasibility and Safety of CT-guided Intrathoracic and Bone Re-biopsy for Non-small Cell Lung Cancer.

This study aimed to retrospectively determine the feasibility and safety of computed tomography (CT)-guided intrathoracic and bone re-biopsy for patients with non-small cell lung cancer (NSCLC). Seventeen patients underwent CT-guided intrathoracic or bone re-biopsy for the determination of epidermal growth factor receptor (EGFR) T790M mutation and/or programmed cell death-ligand 1 (PD-L1) expression. The characteristics of each lesion, success rate of analyses, and complications were investigated. Specimens from 16 out of the 17 patients were adequate for evaluation of EGFR T790M mutation and/or PD-L1 expression. The mean diameter of the lesions was 40 mm, the mean procedural time was 24 minutes, and the median number of punctures was 2. There were no significant differences in lesion characteristics and success rates between CT-guided intrathoracic and bone re-biopsies. No serious complications occurred. Both CT-guided intrathoracic and bone re-biopsies for patients with NSCLC were feasible and safe.

Epidermal growth factor receptor (EGFR) T790M mutation identified in plasma indicates failure sites and predicts clinical prognosis in non-small cell lung cancer progression during first-generation tyrosine kinase inhibitor therapy: a prospective observational study

IntroductionPlasma circulating tumor DNA (ctDNA) is an ideal approach to detecting the epidermal growth factor receptor (EGFR) T790M mutation, which is a major mechanism of resistance to first-generation EGFR-tyrosine kinase inhibitor (TKI) therapy. The present study aimed to explore the association of ctDNA-identified T790M mutation with disease failure sites and clinical prognosis in non-small cell lung cancer (NSCLC) patients.MethodsPatients who progressed on first-generation TKIs were categorized into failure site groups of chest limited (CF), brain limited (BF) and other (OF). Amplification refractory mutation system (ARMS) and droplet digital PCR (ddPCR) were used to identify the T790M mutation in ctDNA. Prognosis was analyzed with Kaplan–Meier methods.ResultsOverall concordance between the two methods was 78.3%. According to both ARMS and ddPCR, patients in the OF group had a significantly higher rate of T790M mutation than did patients in the BF and CF groups (P < 0.001), and a significantly higher T790M mutation rate was also observed in OF-group patients than in those in the CF and BF groups (P < 0.001). AZD9291 was found to be an excellent treatment option and yielded the longest survival for T790M+ patients in all groups who had progressed on EGFR-TKIs; for other treatments, the prognosis of T790M− patient subgroups varied.ConclusionsThe present study demonstrates that T790M mutation in ctDNA is associated with failure sites for NSCLC patients after EGFR-TKI therapy and indicates that both failure site and T790M mutational status greatly influence treatment selection and prognosis.

YH25448, a 3rd generation EGFR-TKI, in patients with EGFR-TKI-resistant NSCLC: Phase I/II study results.

9033Background: The epidermal growth factor receptor (EGFR) T790M mutation is one of the most common acquired resistance mechanism to EGFR tyrosine kinase inhibitors (TKIs). YH25448 is an oral, pot...

The alteration of T790M between 19 del and L858R in NSCLC in the course of EGFR-TKIs therapy: a literature-based pooled analysis.

Treatment-naive epidermal growth factor receptor (EGFR) T790M mutation is more inclined to coexist with L858R than with 19 del in non-small cell lung cancer (NSCLC) patients. However, EGFR-tyrosine kinase inhibitors (EGFR-TKIs) might alter this status. We sought to compare the prevalence of T790M upon acquired resistance to EGFR-TKIs between 19 del and L858R by assembling all existing data. Electronic databases were comprehensively searched for eligible studies. The primary endpoint was the odds ratio (OR) of T790M mutation in NSCLC co-existing with L858R mutation and 19 del upon resistance to first-generation EGFR-TKIs. A random effects model was used. Stratified analysis was performed based on study type (retrospective and prospective), race (Asians and Caucasians) and sample type (tissue and plasma). A total of 25 studies involving 1,770 patients were included. The overall T790M existent rate was 45.25%. Post-resistance T790M was more frequent in 19 del than in L858R mutated patients (53% vs. 36%; OR 1.87; P<0.001). All outcomes of subgroup and overall analyses were similar. In contrast, we re-analyzed the previous meta-analysis, finding that the pooled rate of pretreatment T790M was 14% and 22% in 19 del and L858R respectively (OR 0.59; P<0.001). The increase of T790M rate was 2.79-fold in 19 del and only 0.63-fold in L858R in the course of EGFR-TKIs therapy. Opposite to the situation of de novo T790M, it was observed that T790M was more frequent in exon 19 deletion than in L858R among patients with acquired resistance to EGFR-TKIs. The difference in T790M alteration between 19 del and L858R encourages development of detection or treatment strategies for the specific resistance mechanism.

148P Method comparison for detection of epidermal growth factor receptor (EGFR) T790M mutation in matched biopsied tumour sections and plasma samples

148P Method comparison for detection of epidermal growth factor receptor (EGFR) T790M mutation in matched biopsied tumour sections and plasma samples

Selective gene amplification to detect the T790M mutation in plasma from patients with advanced non-small cell lung cancer (NSCLC) who have developed epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance.

The epidermal growth factor receptor (EGFR) T790M mutation is associated with resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). However, tissues for the genotyping of the EGFR T790M mutation can be difficult to obtain in a clinical setting. The aims of this study were to evaluate a blood-based, non-invasive approach to detecting the EGFR T790M mutation in advanced NSCLC patients using the PointMan™ EGFR DNA enrichment kit, which is a novel method for the selective amplification of specific genotype sequences. Blood samples were collected from NSCLC patients who had activating EGFR mutations and who were resistant to EGFR-TKI treatment. Using cell-free DNA (cfDNA) from plasma, EGFR T790M mutations were amplified using the PointMan™ enrichment kit, and all the reaction products were confirmed using direct sequencing. The concentrations of plasma DNA were then determined using quantitative real-time PCR. Nineteen patients were enrolled, and 12 patients (63.2%) were found to contain EGFR T790M mutations in their cfDNA, as detected by the kit. T790M mutations were detected in tumor tissues in 12 cases, and 11 of these cases (91.7%) also exhibited the T790M mutation in cfDNA samples. The concentrations of cfDNA were similar between patients with the T790M mutation and those without the mutation. The PointMan™ kit provides a useful method for determining the EGFR T790M mutation status in cfDNA.

Intercalated Treatment Following Rebiopsy Is Associated with a Shorter Progression-Free Survival of Osimertinib Treatment.

PurposeEpidermal growth factor receptor (EGFR) T790M mutation serves as an important predictor of osimertinib efficacy. However, little is known about how it works among patients with various timings of T790M emergence and treatment.Materials and MethodsAdvanced EGFR-mutant lung adenocarcinoma patients with positive T790M mutation in tumor were retrospectively enrolled and observed to determine the outcomes of osimertinib treatment. We evaluated the association between patients’ characteristics and the efficacy of osimertinib treatment, particularly with respect to the timing of T790M emergence and osimertinib prescription.ResultsA total of 91 patients were enrolled, including 14 (15.4%) with primary and 77 (84.6%) with acquired T790M mutation. The objective response rate and disease controlratewere 60.9% and 85.1%, respectively. The median progression-free survival (PFS) and overall survival were 11.5 months (95% confidence interval [CI], 9.0 to 14.0) and 30.4 months (95% CI, 11.3 to 49.5), respectively. There was no significant difference in response rate and PFS between primary and acquired T790M populations. In the acquired T790M subgroup, patientswho received osimertinib after T790M had been confirmed by rebiopsy had a longer PFS than those with intercalated treatments between rebiopsy and osimertinib prescription (14.0 months [95% CI, 9.0 to 18.9] vs. 7.2 months [95% CI, 3.7 to 10.8]; adjusted hazard ratio, 0.48 [95% CI, 0.24 to 0.98; p=0.043]). Rebiopsy timing did not influence the outcome.ConclusionOsimertinib prescription with intercalated treatment following rebiopsy but not the timing of T790M emergence influenced the treatment outcome. We suggest that it is better to start osimertinib treatment once T790M mutation has been confirmed by biopsy.

Mechanisms of resistance to irreversible epidermal growth factor receptor tyrosine kinase inhibitors and therapeutic strategies in non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) T790M mutation is the most frequent mechanism which accounts for about 60% of acquired resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients harboring EGFR activating mutations. Irreversible EGFR-TKIs which include the second-generation and third-generation EGFR-TKIs are developed to overcome T790M mediated resistance. The second-generation EGFR-TKIs inhibit the wide type (WT) EGFR combined with dose-limiting toxicity which limits its application in clinics, while the development of third-generation EGFR-TKIs brings inspiring efficacy either in vitro or in vivo. The acquired resistance, however, will also occur and limit their response. Understanding the mechanisms of resistance to irreversible EGFR-TKIs plays an important role in the choice of subsequent treatment. In this review, we show the currently known mechanisms of resistance which can be summarized as EGFR dependent and independent mechanisms and potential therapeutic strategies to irreversible EGFR-TKIs.

Squamous cell transformation and EGFR T790M mutation as acquired resistance mechanisms in a patient with lung adenocarcinoma treated with a tyrosine kinase inhibitor: A case report.

The present case report describes the infrequent coexistence of squamous cell transformation and the epidermal growth factor receptor (EGFR) T790M mutation as resistance mechanisms to first line treatment with tyrosine kinase inhibitors. The patient was a 44-year-old female, diagnosed with a primitive advanced lung adenocarcinoma with bone metastases. The tumor was positive for the EGFR exon 19 deletion, therefore the patient was treated with afatinib (40 mg/day, orally) and radiotherapy for bone lesions. After 16 months, the patient developed resistance. Cytological examination of the pleural effusion confirmed an adenocarcinoma positive for the EGFR exon 19 deletion and the T790M mutation within exon 20, while a biopsy from the upper left bronchus revealed a keratinizing squamous cell carcinoma positive for the EGFR exon 19 deletion. In addition, the EGFR mutations were concomitantly detected in circulating cell-free tumour DNA. Due to the presence of the T790M mutation, the patient underwent osimertinib therapy (80 mg/day, orally), which resulted in a partial tumour regression at the 2-month follow-up, whereas the squamous lesions were treated with radiotherapy. The adenocarcinoma and squamous carcinoma components may share the same origin, according to the presence of the EGFR exon 19 deletion in both lesions. More accurate characterization of resistance mechanisms may lead to the development of improved treatment regimens.

Repeat biopsy of patients with acquired resistance to EGFR TKIs: implications of biopsy-related factors on T790M mutation detection.

To find predictors of non-diagnostic repeat biopsy specimen acquisition for mutational analysis and detection of epidermal growth factor receptor (EGFR) T790M mutation. We retrospectively reviewed 90 non-small cell lung cancer patients harbouring EGFR mutations who underwent repeat cone-beam CT-guided transthoracic needle biopsy. Clinical characteristics as well as biopsy-related factors were compared between patients with and without diagnostic specimen acquisition and between patients with and without T790M mutation. After univariate analysis, multivariate logistic regression analysis was performed to reveal independent predictors. Diagnostic biopsy specimens for mutational test were obtained in 90% (81/90) of patients, of which 62% (50/81) possessed T790M mutation. None of the analysed variables were significantly associated with non-diagnostic specimen acquisition. For T790M detection, duration of EGFR tyrosine kinase inhibitor treatment (p = 0.066), duration of total chemotherapy (p = 0.026), tumour size (p = 0.066), and metastatic lung lesion as a biopsy target (p = 0.029) showed p values less than 0.10. Multivariate analysis revealed that target tumour size (odds ratio, 0.765; p = 0.031) was an independent predictor of T790M mutation. Metastatic lesions as biopsy targets (odds ratio, 4.194; p = 0.050) showed marginal statistical significance. Non-diagnostic repeat biopsy specimen acquisition was not related to the clinical or technical factors. However, detection of T790M at repeat biopsy might be associated with smaller target tumour size and selection of metastatic lesions as biopsy targets. • Cone-beam CT-guided repeat biopsy yielded high diagnostic specimen acquisition rate. • Biopsy-related features were associated with the detection of T790M mutation. • Target tumour size was an independent predictor of the T790M detection. • Biopsy targeting metastatic lung nodules might help detect the T790M mutation.

Epidermal growth factor receptor T790M mutation as a prognostic factor in EGFR-mutant non-small cell lung cancer patients that acquired resistance to EGFR tyrosine kinase inhibitors.

Epidermal growth factor receptor (EGFR) T790M mutation accounted for over half of drug resistance cases in EGFR-mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) and led to different outcomes. This study aimed to assess the prognostic role of T790M in NSCLC patients treated with EGFR-TKIs that developed drug resistance. Eligible literatures were reviewed from various databases and a meta-analysis was performed to evaluate the prognostic role of T790M mutation in EGFR-TKIs treated patients that went progression. Three studies containing 192 patients were included in the meta-analysis. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were 0.66 (95% CI 0.49–0.89, P = 0.007) and 0.53 (95% CI 0.35–0.79, P = 0.002) respectively. Subgroups analyses were also performed on OS and PFS according to patients’ districts, gender and histological type. In conclusion, T790M as a common mutation to cause drug-resistance in EGFR-TKIs treated NSCLC patients may be a favorable prognostic factor on OS and PFS both. Further studies are necessary to demonstrate the prognostic role of secondary T790M in NSCLC patients.

Response to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients with de novo epidermal growth factor receptor (EGFR) T790M and S768I resistance mutations.

e20557 Background: Patients with synchronous de novo EGFR sensitising and resistance mutations are rare. Little is known about the response of these patients to EGFR TKIs, especially in a Caucasian population. Methods: We identified NSCLC patients found to have EGFR mutations using PCR-based fragment length analysis, mass spectrometry-based genotyping (Sequenom), and Sanger sequencing using a large multi-institutional database. Baseline clinical characteristics, response rate, progression free survival (PFS) and overall survival (OS) were calculated. Results: From 2008-2015, we observed de novo synchronous EGFR sensitising and resistance mutations in 12 patients representing an overall incidence of 3.6% of EGFR mutants and 0.4% of all NSCLC patients tested. Seven patients were treated using EGFR TKI therapy with erlotinib. In all cases, T790M (n = 4,50%) or S768I (n = 4, 50%) occurred concurrently with another sensitising EGFR mutation, either L858R (n = 4, 34%) or exon 19 deletion (n = 8, 66%). Objective responses were seen in two patients (29%). Three further patients had stable disease lasting 6, 23 and 54 months respectively. The median progression-free survival was 24 months and the median overall survival was 34 months. All patients with baseline EGFR S768I mutations (n = 3) had an objective response or stable disease on erlotinib while two of four patients with T790M demonstrated de novo resistance. Conclusions: This is the largest Irish review of synchronous de novo EGFR mutations. The incidence of co-occurring EGFR mutations was 0.4% and erlotinib demonstrated activity in this cohort of patients. Ongoing trials will determine whether next-generation EGFR TKIs such as osimertinib are preferable as first-line therapy in these patients.

Meta-analysis of the impact of de novo and acquired EGFR T790M mutations on the prognosis of patients with non-small cell lung cancer receiving EGFR-TKIs.

PurposeThe purpose of this meta-analysis was to explore the influences of pretreatment de novo and posttreatment-acquired epidermal growth factor receptor (EGFR) T790M mutations in patients with advanced non-small cell lung cancer (NSCLC) who had received tyrosine kinase inhibitors (TKIs).MethodsWe searched PubMed, Embase, and the China National Knowledge Infrastructure database for eligible literature. Data were extracted to assess the hazard ratios (HRs) for progression-free survival (PFS), overall survival (OS), and post-progression survival (PPS) and the relative ratios (RRs) for objective response rate (ORR).ResultsThis meta-analysis included 22 studies comprising 1,462 patients with NSCLC who harbored activating EGFR mutations and were treated with EGFR-TKIs. Compared to pretreatment T790M mutation-negative NSCLC, pretreatment T790M mutation-positive NSCLC was associated with decreased PFS (HR 2.23, P<0.001) and OS (HR 1.55, P=0.003). A trend toward significance of worsening ORR (RR 0.86, P=0.051) was evident. The acquired T790M mutation was correlated with improved PFS (HR 0.75, P=0.006) and PPS (HR 0.57, P<0.001), compared to patients without the T790M mutation who progressed after EGFR-TKI treatment. There were no significant differences in OS or ORR between patients with acquired T790M mutation-positive and T790M mutation-negative NSCLC. However, in the tumor tissue rebiopsy subgroup, patients with acquired T790M mutation had improved OS (HR 0.60, P<0.001) compared to T790M mutation-negative patients. In the plasma ctDNA subgroup, acquired T790M mutation decreased the OS (HR 1.87, P<0.001).ConclusionPretreatment T790M mutation was associated with worse PFS and OS in patients with advanced NSCLC treated with EGFR-TKIs, while acquired T790M mutation was associated with longer PFS and PPS than T790M mutation-negative NSCLC. The effects on OS were different between acquired T790M mutation detected from rebiopsy of tumor tissue and that detected from plasma ctDNA.

The prognostic role of pretreatment epidermal growth factor receptor T790M mutation in advanced non-small cell lung cancer patients treated with EGFR tyrosine kinase inhibitors.

PurposeThe outcome of pretreatment epidermal growth factor receptor (EGFR) T790M mutation in EGFR mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) is controversial, this study aimed to evaluate the prognostic role of pretreatment T790M in advanced NSCLC patients treated with EGFR TKIs.ResultsA total of 7 eligible studies containing 179 cases and 281 controls were included in the meta-analysis. The pooled hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were 2.21 (95% CI 1.49-3.29, P<0.001) and 1.24 (95% CI 0.90-1.71, P=0.186), respectively. We also did subgroup analyses on OS and PFS according to patients from various districts.MethodsIdentified literatures from various databases were reviewed. A meta-analysis was performed to evaluate the prognostic role of pretreatment EGFR T790M in advanced EGFR mutant patients treated with EGFR TKIs.ConclusionsPretreatment T790M may be a poor prognostic factor for PFS in advanced NSCLC patients treated with EGFR TKIs. However, no significant prognostic effect was found between pretreatment T790M mutation and OS. More studies are needed to demonstrate the prognostic role of pretreatment T790M mutation in advanced NSCLC patients.