1294P RELAY, erlotinib plus ramucirumab or placebo in untreated EGFR-mutated metastatic NSCLC: Outcomes by EGFR mutation type

Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is a standard treatment in EGFR-mutated advanced non-small-cell lung cancer (NSCLC); however, previous data have suggested that EGFR-TKI has limited potential as adjuvant therapy. On the contrary, based on subset analysis with the immune checkpoint inhibitor (ICI) plus platinum-doublet chemotherapy in advanced NSCLC with EGFR mutation, we hypothesized that this combination was worth testing as adjuvant therapy in patients with EGFR-mutated NSCLC. Methods: Herein, we introduce our phase II study of cisplatin plus vinorelbine combined with atezolizumab as adjuvant therapy for completely resected NSCLC with EGFR mutation. Accrued patients will be pathological stage II–IIIA with completely resected NSCLC and whose tumors have EGFR mutation. Treatment comprises four cycles of cisplatin plus vinorelbine combined with atezolizumab followed by maintenance with atezolizumab. The primary endpoint is the disease-free survival (DFS) rate at 2 years. Secondary endpoints are DFS, overall survival, and safety. In total, 18 patients will be enrolled in this study. Discussion: Ongoing phase III trials of adjuvant ICI allow the inclusion of patients with EGFR mutation, but our current trial will provide the earliest clinical data on the efficacy of platinum-doublet chemotherapy with atezolizumab.

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Emergence of RET rearrangement co-existing with activated EGFR mutation in EGFR -mutated NSCLC patients who had progressed on first- or second-generation EGFR TKI

Lung Cancer ◽

10.1016/j.lungcan.2015.06.021 ◽

2015 ◽

Vol 89 (3) ◽

pp. 357-359 ◽

Cited By ~ 45

Author(s):

Samuel J. Klempner ◽

Lyudmila A. Bazhenova ◽

Fadi S. Braiteh ◽

Petros G. Nikolinakos ◽

Kyle Gowen ◽

...

Keyword(s):

Second Generation ◽

Egfr Mutation ◽

Ret Rearrangement ◽

Nsclc Patients ◽

Egfr Mutated ◽

Egfr Tki

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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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Cell membrane based biomimetic nanocomposites for targeted therapy of drug resistant EGFR-mutated lung cancer

Nanoscale ◽

10.1039/c9nr05791a ◽

2019 ◽

Vol 11 (41) ◽

pp. 19520-19528 ◽

Cited By ~ 9

Author(s):

Pengying Wu ◽

Dongtao Yin ◽

Jiaming Liu ◽

Huige Zhou ◽

Mengyu Guo ◽

...

Keyword(s):

Lung Cancer ◽

Drug Resistance ◽

Targeted Therapy ◽

Cell Membrane ◽

Cancer Cell ◽

Egfr Mutation ◽

Drug Resistant ◽

Egfr Mutated

A cancer cell membrane-based biomimetic strategy was developed by loading doxorubicin and icotinib to overcome drug-resistance of EGFR-mutation lung cancer.

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Tissue and Plasma EGFR Mutation Analysis in the FLAURA Trial: Osimertinib versus Comparator EGFR Tyrosine Kinase Inhibitor as First-Line Treatment in Patients with EGFR-Mutated Advanced Non–Small Cell Lung Cancer

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-19-1126 ◽

2019 ◽

Vol 25 (22) ◽

pp. 6644-6652 ◽

Cited By ~ 18

Author(s):

Jhanelle E. Gray ◽

Isamu Okamoto ◽

Virote Sriuranpong ◽

Johan Vansteenkiste ◽

Fumio Imamura ◽

...

Keyword(s):

Lung Cancer ◽

Egfr Mutation ◽

Kinase Inhibitor ◽

Small Cell ◽

Line Treatment ◽

Small Cell Lung ◽

First Line ◽

Egfr Tyrosine Kinase Inhibitor ◽

Egfr Mutated ◽

First Line Treatment

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Unique MicroRNA and mRNA Interactions in EGFR-Mutated Lung Adenocarcinoma

Journal of Clinical Medicine ◽

10.3390/jcm7110419 ◽

2018 ◽

Vol 7 (11) ◽

pp. 419 ◽

Cited By ~ 3

Author(s):

Sophia Subat ◽

Kentaro Inamura ◽

Hironori Ninomiya ◽

Hiroko Nagano ◽

Sakae Okumura ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Mrna Expression ◽

Regulatory Network ◽

Egfr Mutation ◽

Expression Profiles ◽

Integrative Analysis ◽

Future Research ◽

Mutation Status ◽

Egfr Mutated ◽

Insight Into

The EGFR gene was one of the first molecules to be selected for targeted gene therapy. EGFR-mutated lung adenocarcinoma, which is responsive to EGFR inhibitors, is characterized by a distinct oncogenic pathway in which unique microRNA (miRNA)–mRNA interactions have been observed. However, little information is available about the miRNA–mRNA regulatory network involved. Both miRNA and mRNA expression profiles were investigated using microarrays in 155 surgically resected specimens of lung adenocarcinoma with a known EGFR mutation status (52 mutated and 103 wild-type cases). An integrative analysis of the data was performed to identify the unique miRNA–mRNA regulatory network in EGFR-mutated lung adenocarcinoma. Expression profiling of miRNAs and mRNAs yielded characteristic miRNA/mRNA signatures (19 miRNAs/431 mRNAs) in EGFR-mutated lung adenocarcinoma. Five of the 19 miRNAs were previously listed as EGFR-mutation-specific miRNAs (i.e., miR-532-3p, miR-500a-3p, miR-224-5p, miR-502-3p, and miR-532-5p). An integrative analysis of miRNA and mRNA expression revealed a refined list of putative miRNA–mRNA interactions, of which 63 were potentially involved in EGFR-mutated tumors. Network structural analysis provided a comprehensive view of the complex miRNA–mRNA interactions in EGFR-mutated lung adenocarcinoma, including DUSP4 and MUC4 axes. Overall, this observational study provides insight into the unique miRNA–mRNA regulatory network present in EGFR-mutated tumors. Our findings, if validated, would inform future research examining the interplay of miRNAs and mRNAs in EGFR-mutated lung adenocarcinoma.

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Clinical significance of monitoring EGFR mutation in plasma using multiplexed digital PCR in EGFR mutated patients treated with afatinib (West Japan Oncology Group 8114LTR study)

Lung Cancer ◽

10.1016/j.lungcan.2019.03.021 ◽

2019 ◽

Vol 131 ◽

pp. 128-133 ◽

Cited By ~ 7

Author(s):

Hiroaki Akamatsu ◽

Yasuhiro Koh ◽

Isamu Okamoto ◽

Daichi Fujimoto ◽

Akihiro Bessho ◽

...

Keyword(s):

Clinical Significance ◽

Egfr Mutation ◽

Digital Pcr ◽

Oncology Group ◽

Egfr Mutated

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Retreatment with Erlotinib of a Patient with Metastatic NSCLC Harboring EGFR Mutation: A Case Report

Tumori Journal ◽

10.1177/1578.17234 ◽

2014 ◽

Vol 100 (3) ◽

pp. e70-e73 ◽

Cited By ~ 1

Author(s):

Ondrej Fiala ◽

Milos Pesek ◽

Jindrich Finek ◽

Gabriela Krakorova ◽

Lucie Benesova ◽

...

Keyword(s):

Case Report ◽

Egfr Mutation ◽

Metastatic Nsclc

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Interim analysis of afatinib monotherapy in patients with metastatic NSCLC progressing after chemotherapy and erlotinib/gefitinib (E/G) in a trial of afatinib plus paclitaxel versus investigator’s choice chemotherapy following progression on afatinib monotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.7557 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 7557-7557 ◽

Cited By ~ 11

Author(s):

Martin H. Schuler ◽

David Planchard ◽

James Chih-Hsin Yang ◽

Joo-Hang Kim ◽

Filippo De Marinis ◽

...

Keyword(s):

Tyrosine Kinases ◽

Interim Analysis ◽

Egfr Mutation ◽

Acquired Resistance ◽

Phase Iii ◽

Open Label ◽

Logrank Test ◽

Metastatic Nsclc ◽

Best Response ◽

Egfr Tkis

7557 Background: The benefit of sustained ErbB family blockade in NSCLC patients with acquired resistance (AR) to EGFR TKIs is unknown. We investigated afatinib, an irreversible blocker of EGFR (ErbB1), HER2 (ErbB2) and ErbB4 receptor tyrosine kinases, in patients with metastatic NSCLC, who had failed chemotherapy and E/G. Methods: This was a Phase III, randomized, open-label, multi-center trial. Patients with pathologically confirmed Stage IIIB/IV metastatic NSCLC after ≥1 line of chemotherapy who failed E/G received oral afatinib 50 mg until disease progression (Part A). After progression, patients with clinical benefit (≥12 wks) were eligible to continue afatinib 40 mg plus paclitaxel or receive investigator’s choice chemotherapy (Part B). Primary endpoint for Part A was PFS (RECIST 1.1; CT scan every 6 wks). Available tumor samples were collected for central EGFR mutation testing; local mutation data were also collected. An interim analysis of Part A, assessing afatinib monotherapy, is reported. Results: Part A enrolled April 2010 through to May 2011; 1154 patients received afatinib monotherapy. The majority had adenocarcinoma (85%), 57% were female, 43% were Asian, 54% were never smokers. Best response to prior E/G was CR (2%), PR (31%), SD (42%) and PD (20%). Median PFS for afatinib was 3.3 mths; 88 patients (8%) achieved an objective tumor response, 648 (56%) had SD. For EGFR mutation positive patients (n=49, centrally confirmed), PFS was 4.2 vs. 2.6 mths for EGFR mutation negative patients (n=35). When applying clinical enrichment criteria for AR, PFS was 4.2 mths for those with enrichment (n=597) vs. 2.8 mths for those without (n= 557; logrank test p<0.0001). The most common grade 3/4 adverse events were diarrhea (17%) and rash/acne (11%). In Part A, 99 patients remain on treatment. Conclusions: Afatinib monotherapy provided a clinically meaningful benefit in this large, treatment-refractory NSCLC trial, similar to LUX-Lung 1. Those clinically enriched for AR to EGFR TKIs achieved prolonged disease control upon continued ErbB blockade.

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