scholarly journals Complete Response to Afatinib of an EGFR Exon 18 delE709_T710insD-Mutated Stage IV Lung Adenocarcinoma

2021 ◽  
Author(s):  
Blandine Jelli ◽  
Olivier Taton ◽  
Nicky D'Haene ◽  
Myriam Remmelink ◽  
Zita Mekinda
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Complete Response ◽  
Egfr Mutations ◽  
First Case ◽  
Treatment Interruptions ◽  
Patient Prognosis ◽  
Lung Adenocarcinomas

Introduction: Epidermal growth factor receptor (EGFR) mutations are frequently found in patients with lung adenocarcinomas, 90% being deletions in exon 19 or point mutation in exon 21. Three generations of tyrosine kinase inhibitors (TKIs) targeting EGFR mutations are available and have changed patient prognosis but less data is available on exon 18 mutations and their sensitivity to TKI therapy. Exon 18 delE709_T710insD accounts for 0.06% (16/27,294) of all EGFR mutations and is an oncogenic driver. Several partial responses to afatinib have been described. Case description: We report the first case, to the best of our knowledge, of the complete response to afatinib of a 57-year-old patient with stage IV lung adenocarcinoma with a delE709_T710insD mutation in the EGFR gene detected by next-generation sequencing. Oral afatinib was prescribed and despite treatment interruptions and dosage tapering due to cutaneous adverse events, a complete response was achieved 12 months after treatment initiation and is currently maintained at 17 months. Conclusion: When EGFR mutation is suspected, complete DNA sequencing of exons 18 to 21 should be carried out and we suggest that afatinib should be the first-line treatment for exon 18 delE709_T710insD-mutated advanced lung adenocarcinomas.

scholarly journals Better Progression-Free Survival in Elderly Patients with Stage IV Lung Adenocarcinoma Harboring Uncommon Epidermal Growth Factor Receptor Mutations Treated with the First-line Tyrosine Kinase Inhibitors

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 434 ◽  
Author(s):  
Ming-Ju Tsai ◽  
Jen-Yu Hung ◽  
Mei-Hsuan Lee ◽  
Chia-Yu Kuo ◽  
Yu-Chen Tsai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
First Line ◽  
Free Survival ◽  
Younger Patients ◽  
Epidermal Growth

Patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutations usually have a good response rate (RR) and longer progression-free survival (PFS) to EGFR tyrosine kinase inhibitors (TKIs). However, the treatment efficacy to uncommon EGFR mutations remains controversial. We, therefore, performed a retrospective study, screening 2958 patients. A total of 67 patients with lung adenocarcinoma harboring uncommon EGFR mutations were enrolled and 57 patients with stage IV diseases receiving a first-line EGFR TKI were included for further analyses. The patients were classified into 27 (47%) “a single sensitizing uncommon mutation”, 7 (12%) “multiple sensitizing mutations”, 5 (9%) “a sensitizing mutation and a resistant uncommon mutation”, and 18 (32%) “other resistant uncommon mutations”. No significant difference was noted in PFS or overall survival (OS) between groups. Patients receiving different first-line EGFR TKIs had similar PFS and OS. The elder patients had a significantly poorer performance status than the younger patients but a significantly longer PFS than the younger patients (median PFS: 10.5 vs. 5.5 months, p = 0.0320). In conclusion, this is the first study to identify that elderly patients with stage IV lung adenocarcinoma harboring uncommon EGFR mutation might have a longer PFS. Large-scale prospective studies are mandatory to prove our findings.

scholarly journals Achievement of Cure with Gefitinib in Advanced Lung Adenocarcinoma Harboring an Activating EGFR Mutation: A Case Report

2016 ◽  
Vol 9 (3) ◽  
pp. 565-567 ◽  
Author(s):  
Taiji Kuwata ◽  
Kazue Yoneda ◽  
Kenichi Kobayashi ◽  
Rintarou Oyama ◽  
Hiroki Matumiya ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Term Survival ◽  
Activating Mutations ◽  
First Case ◽  
Old Japanese ◽  
Gefitinib Treatment ◽  
Activating Egfr Mutation

Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) may achieve long-term survival in selected cases with advanced non-small cell lung cancer harboring activating mutations in the EGFR gene, but a cured case has not been reported yet. Here, we present the first case of EGFR-mutated lung adenocarcinoma cured with an EGFR-TKI, as the 75-year-old Japanese man has achieved complete response with gefitinib treatment and has survived without tumor 10 years after termination of gefitinib treatment.

Lung Cancer in 2013: State of the Art Therapy for Metastatic Disease

2013 ◽  
pp. 339-346
Author(s):  
Frances A. Shepherd ◽  
Paul A. Bunn ◽  
Luis Paz-Ares
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Poor Performance ◽  
Initial Therapy ◽  
Egfr Mutations ◽  
Molecular Testing ◽  
Molecular Features ◽  
Platinum Doublet

Lung cancer is the leading worldwide cause of cancer death and the majority of patients present with metastatic stage IV disease. At diagnosis, clinical, histologic, and molecular features must be considered in therapeutic decision-making for systemic therapy. Molecular testing for at least epidermal growth factor receptor ( EGFR) and ALK should be performed in all patients before therapy. Platinum doublet chemotherapy may be considered for “fit” patients who do not have a molecular driver genetic abnormality. Bevacizumab can be considered for addition to the doublet in patients with nonsquamous cancers who have no contraindications. A pemetrexed combination is considered only in nonsquamous histology. Patients with EGFR mutations or ALK fusions should be treated with erlotinib or crizotinib, respectively, even in patients with tumor-related poor performance. The tyrosine-kinase inhibitors (TKIs) may be continued until multisite, symptomatic progression. For patients initially treated with a platinum doublet, maintenance chemotherapy with pemetrexed, erlotinib, gemcitabine, or possibly docetaxel is an option with selection based on clinical features, histology, type of initial therapy, and response to first-line therapy.

scholarly journals Bone Metastasis of Non-Small-Cell Lung Cancer Showing Pathological Complete Response to Osimertinib Monotherapy

2021 ◽  
pp. 1876-1881
Author(s):  
Hiroshi Shintani ◽  
Shoji Oura ◽  
Tomoyuki Yamaguchi ◽  
Shinichiro Makimoto
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Pathological Complete Response ◽  
Lung Nodule ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Pathological Examination ◽  
The Right

A 70-year-old man with lung adenocarcinoma had undergone right lower lobectomy and lymph node dissection. Only 6 months later under adjuvant uracil and futraful therapy, the patient developed a solitary bone metastasis in the right 8th rib. Due to positive mutation of epidermal growth factor receptor (EGFR) exon 21 L858R in the primary cancer, the patient received osimertinib monotherapy, leading to massive calcification of the osteolytic bone metastasis with significant decrease of standard uptake value on positron emission tomography. After 12 months of osimertinib monotherapy, slight enlargement of the ground glass nodule, i.e., presumed noninvasive lung cancer, in the right upper lobe, and no further occurrence of metastatic foci made us to resect both the lung nodule and the bone metastasis. Pathological examination showed the lung nodule to be noninvasive adenocarcinoma and the bone metastasis to have no viable cancer cells. The patient was discharged on the 8th postoperative day without any complication. On developing a therapeutic strategy for advanced/recurrent EGFR mutation-positive lung adenocarcinoma, oncologists should note the possibility of pathological complete response to newly developed EGFR tyrosine kinase inhibitors including osimertinib for a presumed cure of oligometastatic lung adenocarcinoma.

scholarly journals Neoadjuvant EGFR-TKI Therapy for EGFR-Mutant NSCLC in Traditionally Unresectable Patients

2021 ◽  
Author(s):  
Ke-Cheng Chen ◽  
Shuenn-Wen Kuo ◽  
Chen-Hao Hsiao ◽  
Jing-Shing Chen
Keyword(s):  
Thoracic Surgery ◽  
Lung Adenocarcinoma ◽  
Surgical Resection ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Multidisciplinary Management ◽  
Advanced Stage ◽  
Nsclc Patients

Abstract IntroductionAdvanced stage non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations may have benefit from tyrosine kinase inhibitors (TKI). However, the role of multidisciplinary management including neoadjuvant TKI therapy and thoracic surgery is uncertain. This study assessed the possible impact of neoadjuvant TKI therapy and thoracic surgery in selected advanced stage patients.MethodsAdvanced stage of IIIB and IVA NSCLC patients were retrospectively reviewed from 2010 to 2013. Patients with EGFR mutations who received neoadjuvant TKI followed by surgical resection were included. All patients were followed up for 5 years or until death.ResultsThere were total 15 advanced stage lung adenocarcinoma patients in the study. 8 patients were stage IIIB and 7 were stage IVA. All tumor sizes significantly decreased after neoadjuvant TKI therapy (p value = 0.0002). 11 patients received adjuvant TKI therapy after surgical resection and others received adjuvant cisplatin-based chemotherapy. Progression-free survival was superior in the group of adjuvant TKI therapy than in the group of adjuvant chemotherapy (median 14 months versus 5.9 months, p value = 0.016). Overall survival (OS) was not different between two groups (p value = 0.755). In the group of adjuvant TKI therapy, median OS in patients harboring exon 19 deletion and exon 21 L858R was 60 months and 44.9 months, respectively (p value = 0.078). ConclusionTKI may decrease the size of EGFR mutation lung adenocarcinoma. A multidisciplinary management including neoadjuvant TKI therapy and thoracic surgery may be discussed in selected advanced stage lung adenocarcinoma.

RET rearrangements detected by FISH in “pan-negative” lung adenocarcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8024-8024 ◽  
Author(s):  
Marileila Varella-Garcia ◽  
Liang Guo Xu ◽  
Sakshi Mahale ◽  
Eamon M Berge ◽  
Chiara Bennati ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Molecular Subtype ◽  
Stage Iv ◽  
Stage Iv Disease ◽  
Heavily Pretreated ◽  
Target Fish ◽  
Never Smokers ◽  
Practice Methods ◽  
Lung Adenocarcinomas

8024 Background: RET rearrangements have recently been reported in NSCLC and there is pre-clinical evidence that RET tyrosine kinase inhibitors (TKIs) block activated RET kinase. Efficient and accurate detection of RET rearrangements are crucial for the success of RET TKIs in clinical trials. RET rearrangements have been detected by specialized sequencing techniques with limited applicability to clinical practice. Methods: A 3-target FISH probe set was developed to detect KIF5B-RET fusions and identify patterns suggestive of RET rearrangements with non-KIF5B partners. 51 lung adenocarcinomas negative for EGFR, KRAS, ALK and ROS1 (36 were also negative for 7 other molecular markers) were investigated. Clinical and demographic characteristics were collected. Results: Eight patients (15%) had rearrangements in the RET gene: 5 with KIF5B-RET fusions, 2 with patterns consistent with the CCDC6-RET fusion, and 1 with extra copies of single 3’RET (loss of 5’RET). Atypical FISH patterns were detected both in RET + and negative specimens suggesting high genomic instability in the KIF5B – RET region. RT-PCR assay determined the exon/fusion variant in 4 cases including 2 patients with K15:R12, 1 with K16:R12 and 1 with C1:R12. Median age at diagnosis was 58.5 in the mutation negative and 63 in the RET+ patients. Both cohorts were predominantly male (66% and 56%, respectively), with a majority of never smokers (59 and 89%, respectively), and stage IV disease at diagnosis (72 and 89%, respectively). Two heavily pretreated RET+ patients had stable disease at their initial restaging scans following treatment with the RET inhibitor vandetanib (radiographic assessment per RECIST 1.1); two others had early radiographic progression with sunitinib. Conclusions: The FISH probe proved efficient to detect RET rearrangements in lung adenocarcinomas, involving KIF5B and non-KIF5B partners. Frequency of RET rearrangements in this enriched lung adenocarcinoma cohort was considerably higher than reported in unselected cohorts. Further molecular analyses are being performed to increase understanding of the natural history of this new molecular subtype of NSCLC. Support: B J Addario Foundation, NCI P50CA058187, NCI CCSG P30CA046934.

scholarly journals EGFR-Mutated Squamous Cell Lung Cancer and Its Association With Outcomes

2021 ◽  
Vol 11 ◽  
Author(s):  
Rui Jin ◽  
Ling Peng ◽  
Jiawei Shou ◽  
Jin Wang ◽  
Yin Jin ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Squamous Cell ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Lung Squamous Cell Carcinoma ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Wild Type ◽  
Egfr Tki ◽  
Egfr Tkis

BackgroundThe therapeutic efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced EGFR-mutant lung squamous cell carcinoma (SCC) patients remains uncertain. Furthermore, the factors underlying the responsiveness have not been fully investigated. We therefore investigated the link between genomic profiles and EGFR-TKI efficacy.Material and MethodsWe consecutively enrolled stage IV, EGFR-mutant, and EGFR-TKI–treated patients with SCC. Patients with EGFR wild-type lung SCC and EGFR-mutant lung adenocarcinoma were consecutively enrolled as controls, and next-generation sequencing (NGS) was performed.ResultsIn total, 28 EGFR-mutant lung SCC, 41 EGFR-mutant lung adenocarcinoma, and 40 EGFR wild-type lung SCC patients were included. Among the patients with EGFR mutations, shorter progression-free survival (PFS) was observed in SCC compared to adenocarcinoma (4.6 vs. 11.0 months, P<0.001). Comparison of the genomic profiles revealed that EGFR-mutant SCC patients had similar mutation characteristics to EGFR-mutant adenocarcinoma patients, but differed from those with EGFR wild-type SCC. Further exploration of EGFR-mutant SCC revealed that mutations in CREBBP (P = 0.005), ZNF217 (P = 0.016), and the Wnt (P = 0.027) pathway were negatively associated with PFS. Mutations in GRM8 (P = 0.025) were associated with improved PFS.ConclusionsEGFR-mutant lung SCC has a worse prognosis than EGFR-mutant adenocarcinoma. Mutations in other genes, such as CREBBP, ZNF217, GRM8, or Wnt that had implications on PFS raise the possibility of understanding mechanisms of resistance to EGFR-TKI in lung SCC, which will aid identification of potential beneficial subgroups of patients with EGFR-mutant SCCs receiving EGFR-TKIs.

Sign in / Sign up

Export Citation Format

Share Document