ΔCT value of amplified refractory mutation system (ARMS) to predict efficacy of EGFR-TKIs in non-small cell lung cancer: A multicenter retrospective study.

e20573 Background: This multi-center retrospective study was to determine whether the ΔCt value of Amplified Refractory Mutation System (ARMS) in EGFR mutated detection in tumors predicts the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small-cell lung cancer (NSCLC). Methods: A total of 108 NSCLC patients harbored an exon 19 deletion (19Del) or exon 21 L858R mutation detected by ARMS were enrolled. We identified patients with ΔCt<1(Group L) harbored a high proportion of EGFR mutation but the patients with ΔCt≥1 (Group H) harbored a low proportion of EGFR mutation in the tumor sample. The progression-free survival (PFS), objective response rates (ORRs) and overall survival (OS) between the groups were analyzed. Results: In the 108 patients we enrolled, 63 were in group L and 45 were in group H. Patients’ demographics and clinical characteristics including age, sex, smoking history, pathology, mutation sites, TNM stage, line of TKIs therapy were not significantly difference between group L and group H. The Median PFS was 331 days (95%CI: 311.8 to 350.2) in group L and 206 days (95%CI, 157.2 to 254.8) in group H and the difference showed statistically significant (P < 0.001). Moreover, the ORRs in group L was significant higher than the group H (60.0% vs 34.9%, P = 0.011). The median OS was 744 days (95%CI, 635.5 to 852.5) in group L and 596 days in group H (95%CI, 491.7 to 700.0) but showed not statistically significant ( P = 0.098). Conclusions: ΔCt value of ARMS in EGFR mutated detection could be an efficacy predictor for EGFR-TKIs treatment in advanced EGFR-mutant NSCLC.

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ΔCT Value of Amplified Refractory Mutation System Predicts Efficacy of EGFR-TKIs in Advanced Non–Small-Cell Lung Cancer: A Multi-Center Retrospective Study

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.684661 ◽

2021 ◽

Vol 8 ◽

Author(s):

Min Chen ◽

Wenqi Huang ◽

Dongyong Yang ◽

Jincheng Huang ◽

Gong Li ◽

...

Keyword(s):

Lung Cancer ◽

Retrospective Study ◽

Small Cell ◽

Rank Test ◽

Small Cell Lung ◽

Log Rank Test ◽

Mutation System ◽

Residuals Analysis ◽

Egfr Mutant ◽

Egfr Tkis

Purpose: This multi-center retrospective study determines whether the ΔCT value of the Amplified Refractory Mutation System (ARMS) predicts the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant advanced non–small-cell lung cancer (NSCLC).Patients and methods: Patients who harbored an exon 19 deletion (19Del) or L858R mutation detected by the ARMS and previously received treatment of EGFR-TKIs as a monotherapy were enrolled. A total of 108 NSCLC patients in four hospitals were enrolled. We divided the patients into a high ΔCT group (Group H) and a low ΔCT group (Group L) by the Martingale residuals analysis and log-rank test. The primary outcome was progression-free survival (PFS). Univariate analysis and multivariable regression were applied to compare the PFS between the groups.Result: The Martingale residuals analysis and log-rank test were applied to find the cutoff ΔCT value (0.8). In the 108 patients we enrolled, 59 were in group L and 49 were in group H. Patients’ demographics and clinical characteristics, including age, sex, smoking history, pathology, mutation sites, TNM stage, and line of TKIs therapy, were not significantly different between group L and group H. The median PFS was 11.1 months in group L and 6.9 months in group H, and the difference showed statistical significance (p < 0.001). Moreover, the objective response rates (ORRs) in group L was significantly higher than in group H (61.0 vs 34.7%, p = 0.002). The median OS was 25.0 months in group L and 20.0 months in group H (p = 0.046).Conclusion: The ΔCT value of ARMS could be an efficacy predictor for EGFR-TKI treatment in advanced EGFR-mutant NSCLC.

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A real world analysis of first line treatment of advanced EGFR mutated non-small cell lung cancer: A multi-center, retrospective study

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211020798 ◽

2021 ◽

pp. 107815522110207

Author(s):

Chung-Shien Lee ◽

Iman Ahmed ◽

Emily Miao ◽

Shirley Chung ◽

Khilna Patel ◽

...

Keyword(s):

Lung Cancer ◽

Retrospective Study ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Front Line ◽

Small Cell Lung ◽

Egfr Mutated ◽

Egfr Tki ◽

Egfr Tkis

Introduction The recently published FLAURA trial demonstrated that osimertinib has remarkable efficacy in front-line setting for non-small cell lung cancer (NSCLC). While this has transformed current practice, there are no effective treatments following progression on osimertinib. The aim of our study was to compare progression-free survival (PFS) and overall survival (OS) between patients initiated on osimertinib to those started on other EGFR TKIs. Methods This was a multicenter, retrospective study conducted at two large academic centers. Adult patients with EGFR-mutated non-small cell lung cancer (NSCLC) who received EGFR therapy between 2014 and 2019 were included. Patients were dichotomized based on front-line TKI (osimertinib vs. other). PFS, OS, and time-to-discontinuation were evaluated. Results One-hundred seventy-two patients were included in the final analysis. Fifty-two (30.2%) patients received osimertinib and 120 (69.8%) patients received another EGFR TKI. The PFS rates at 6, 12, and 18 months were 86.3%, 79.5%, 69.8% in the osimertinib group and 86.6%, 64.2%, 39.3% in the other EGFR TKI group, respectively (p < 0.0036).Estimated OS at 6, 12, and 18 months was similar for both groups: 94.2%, 94.2%, 80.2% and 95.7%, 93.9%, 84.1%, respectively [Adjusted HR = 0.95 (95% CI, 0.37–2.44; p < 0.9128]. Conclusion Osimertinib demonstrated greater 12 and 18 month PFS compared to other EGFR TKIs. This finding is consistent with results of the FLAURA trial. However, unlike FLAURA, there were no differences in estimated OS between the two groups in our study. Further research to evaluate optimal sequencing strategies in the real world of first, second and third generation TKIs is needed.

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Predictive value of pretreatment PD-L1 expression in EGFR-mutant non-small cell lung cancer: a meta-analysis

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02254-x ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Zhiyu Peng ◽

Huahang Lin ◽

Ke Zhou ◽

Senyi Deng ◽

Jiandong Mei

Keyword(s):

Lung Cancer ◽

Sensitivity Analysis ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Predictive Value ◽

Meta Analysis ◽

Small Cell ◽

Small Cell Lung ◽

Egfr Mutant ◽

Egfr Tkis

Abstract Objective To investigate the predictive value of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Methods We conducted a systemic search of PubMed, EMBASE, and the Cochrane Library from 1 January 2000 to 30 August 2020, to identify related studies. We combined the hazard ratio (HR) and 95% confidence interval (CI) to assess the correlation of PD-L1 expression with progression-free survival (PFS) and overall survival (OS). We assessed the quality of the included studies by the Newcastle–Ottawa Scale (NOS). We performed subgroup analyses based on immunohistochemistry (IHC) scoring system, IHC antibodies, sample size, countries, and survival analysis mode. Sensitivity analysis and evaluation of publication bias were also performed. Results Twelve studies including 991 patients met the criteria. The mean NOS score was 7.42 ± 1.19. Patients with high PD-L1 expression was associated with poorer PFS (HR = 1.90; 95% CI = 1.16–3.10; P = 0.011), while there was no association between PD-L1 expression and OS (HR = 1.19; 95% CI = 0.99–1.43; P = 0.070). Subgroup analysis prompted IHC scoring systems, IHC antibodies, and sample size have important effects on heterogeneity. The pooled results were robust according to the sensitivity analysis. Conclusions The result of this meta-analysis suggested that PD-L1 expression might be a predictive biomarker for EGFR-mutant non-small cell lung cancer treated with EGFR-TKIs.

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Adjuvant gefitinib versus cisplatin/vinorelbine in Japanese patients with completely resected, EGFR-mutated, stage II-III non-small cell lung cancer (IMPACT, WJOG6410L): A randomized phase 3 trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8501 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 8501-8501

Author(s):

Hirohito Tada ◽

Tetsuya Mitsudomi ◽

Takeharu Yamanaka ◽

Kenji Sugio ◽

Masahiro Tsuboi ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Egfr Mutation ◽

Disease Free Survival ◽

Small Cell ◽

Stage Ii ◽

Small Cell Lung ◽

Significant Difference ◽

Egfr Mutated

8501 Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor is a standard of care for EGFR mutation-positive, untreated metastatic non-small cell lung cancer (NSCLC). However, the efficacy and safety of adjuvant gefitinib for patients with completely resected lung cancer harboring EGFR mutation over cisplatin-based adjuvant chemotherapy were not known in 2011 when this study was initiated. Methods: From September 2011 to December 2015, we randomly assigned 234 patients with completely resected, EGFR mutation-positive (exon 19 deletion or L858R), stage II–III NSCLC to receive either gefitinib (250 mg, once daily) for 24 months or cisplatin (80 mg/m2 on day 1) plus vinorelbine (25 mg/m2 on days 1 and 8) (cis/vin) every 3 weeks for four cycles. The primary endpoint was disease-free survival (DFS) according to a central review in the intent-to-treat (ITT) population. Results: Two patients in the gefitinib arm withdrew consent and were excluded from the ITT population. No treatment-related deaths were seen in the gefitinib arm, but three treatment-related deaths were reported in the cis/vin arm. Median duration of follow-up was 71 months. Median DFS was numerically longer in the gefitinib arm (36 months) than in the cis/vin arm (25.2 months). However, Kaplan-Meier curves began to overlap around 5 years after surgery, and no significant difference in DFS was seen, with a hazard ratio (HR) of 0.92 (95% confidence interval (CI), 0.67–1.28; P = 0.63). Overall survival was also not significantly different (median not reached in either arm). Five-year survival rates for gefitinib and cis/vin arms were 78.0% and 74.6%, respectively, with an HR for death of 1.03; 95%CI, 0.65–1.65; P = 0.89. Exploratory subset analysis revealed that patients ³70 years old in the gefitinib arm (n = 19/27 with G to cis/vin) survived longer than those in the cis/vin arm (HR 0.31; 95%CI, 0.10–0.98; P = 0.046). Conclusions: Adjuvant gefitinib appeared to prevent early relapse, but did not significantly prolong DFS or OS in patients with completely resected stage II–III, EGFR-mutated NSCLC. The apparent non-inferiority of DFS/OS may justify the use of adjuvant gefitinib in selected subset of patients, especially those deemed unsuitable for cis/vin adjuvant therapy. Clinical trial information: UMIN000006252.

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