Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu

Grève, Jacques De; Teugels, Erik; Geers, Caroline; Decoster, Lynn; Galdermans, D.; Mey, Johan De; Everaert, Hendrik; Umelo, Ijeoma Adaku; Veld, Peter In’t; Schallier, Denis

doi:10.1016/j.lungcan.2012.01.008

Cited by 246 publications

(163 citation statements)

References 19 publications

(20 reference statements)

Supporting

Mentioning

154

Contrasting

Unclassified

Order By: Relevance

“…The mutant cells [28] and patients [31] exhibited exquisite sensitivity to the irreversible dual-specificity EGFR/ERBB2 kinase inhibitor BIBW2992, afatinib. Trastuzumab-besed therapies effective cases were previously reported [30]. However in our cohort, only one case had Hercep Test 1+.…”

Section: Page -03mentioning

confidence: 49%

See 1 more Smart Citation

Extracellular Domain Mutation of ErbB2 Status in Japanese Lung Cancer Patients

2013

J Oncobiomark

View full text Add to dashboard Cite

Purpose: The erbB pathway involves a family of tyrosine kinases and has contributed to resistance or sensitivity for chemotherapy in many tumor types. Somatic mutations of the erbB family receptor gene at kinase domain were found in lung cancer patients. However, the incidence of extracellular domain mutation of erbB2 in Japanese patients has been rarely described. We report on the incidence of these mutations and clinical factors associated with these mutations. Material and Methods:We have investigated extracellular domain mutations of erbB2 status in non-small cell lung cancer (NSCLC) patients by reverse transcript polymerase chain reaction (RT-PCR) and direct sequencing. The study included 210 surgically removed EGFR or ALK gene wild type lung cancer cases from Nagoya City University Hospital. Results:One G309E erbB2 mutation case was found from squamous cell carcinoma. Within adenocarcinoma, no erbB2 mutation was found in extracellular domain. We have previously detected six erbB2 mutations at kinase domain all in adenocarcinomas. Among the 7 erbB2 gene mutation cases, one case with kinase domain mutation was Hercep test positive. Conclusion:The extracellular domain mutation of erbB2 was rare in Japanese population. Although this mutation is rare, its identification could result in more precise treatment of patients.

show abstract

Section: Page -03mentioning

confidence: 49%

“…It has shown that the common erbB2 mutation, A775insYVMA, lead to oncogenic transformation in a cellular assay [23]. Because one co-existed case with erbB2 and Kras mutation was reported [30], we have also examined the Kras mutant cases. However, in our cohort, Kras and erbB2 mutations were exclusive.…”

Section: Page -03mentioning

confidence: 99%

Extracellular Domain Mutation of ErbB2 Status in Japanese Lung Cancer Patients

2013

J Oncobiomark

View full text Add to dashboard Cite

show abstract

“…Although anti-Her2 therapies are ineffective in HER2-amplified NSCLC [98,99] , HER2-mutant NSCLC has been shown to be responsive to trastuzumab plus chemotherapy, with an overall response rate of 50% and median PFS of 5.1 mo in one case series [96] . Afatinib, the ErbB family inhibitor approved for EGFR-mutant NSCLC as discussed earlier in this review, also has clinical activity against HER2-mutant NSCLC in a small case series [96,100] . As HER family members signal via the PI3K-AKT-mTOR cascade, recent attempts have been made to inhibit both HER2 and mTOR in HER2-driven cancers.…”

Section: Other "Actionable" Molecular Targetsmentioning

confidence: 96%

Review of the current targeted therapies for non-small-cell lung cancer

Nguyen

Neal

Wakelee

2014

WJCO

View full text Add to dashboard Cite

The last decade has witnessed the development of oncogene-directed targeted therapies that have significantly changed the treatment of non-small-cell lung cancer (NSCLC). In this paper we review the data demonstrating efficacy of gefitinib, erlotinib, and afatinib, which target the epidermal growth factor receptor (EGFR), and crizotinib which targets anaplastic lymphoma kinase (ALK). We discuss the challenge of acquired resistance to these small-molecular tyrosine kinase inhibitors and review promising agents which may overcome resistance, including the EGFR T790M-targeted agents CO-1686 and AZD9291, and the ALKtargeted agents ceritinib (LDK378), AP26113, alectinib (CH/RO5424802), and others. Emerging therapies directed against other driver oncogenes in NSCLC including ROS1 , HER2 , and BRAF are covered as well.The identification of specific molecular targets in a significant fraction of NSCLC has led to the personalized deployment of many effective targeted therapies, with more to come. Key words: Lung cancer; Non-small cell lung cancer; Targeted therapies; Epidermal growth factor receptor; Epidermal growth factor receptor; Anaplastic lymphoma kinase; Anaplastic lymphoma kinase; Acquired resistance Core tip: The development of oncogene-directed targeted therapies has significantly changed the treatment of non-small-cell lung cancer. We review the data demonstrating efficacy of small-molecule tyrosine kinase inhibitors against epidermal growth factor receptor, anaplastic lymphoma kinase, ROS1, and other oncogenes. We also discuss the challenge of acquired resistance to these therapies and review promising agents which may overcome resistance.Nguyen KSH, Neal JW, Wakelee H. Review of the current targeted therapies for non-small-cell lung cancer.

show abstract

“…Several TKIs are being tested in HER2-dependent lung adenocarcinomas. A phase II trial of the EGFR/HER2 dual inhibitor afatinib showed responses in three of five pretreated patients with advanced NSCLC with prospectively identified HER2 mutations (35). The preliminary results from an ongoing phase II trial of dacomitinib, another oral pan-HER irreversible TKI, described three responses out of 18 evaluable patients with HER2-mutant NSCLC (NCT00818441) (8).…”

Section: Her2 Amplification and Insertionsmentioning

confidence: 99%

The Impact of Genomic Changes on Treatment of Lung Cancer

Cardarella

Johnson

2013

Am J Respir Crit Care Med

View full text Add to dashboard Cite

The remarkable success of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors in patients with EGFR mutations and ALK rearrangements, respectively, introduced the era of targeted therapy in advanced non-small cell lung cancer (NSCLC), shifting treatment from platinum-based combination chemotherapy to molecularly tailored therapy. Recent genomic studies in lung adenocarcinoma identified other potential therapeutic targets, including ROS1 rearrangements, RET fusions, MET amplification, and activating mutations in BRAF, HER2, and KRAS in frequencies exceeding 1%. Lung cancers that harbor these genomic changes can potentially be targeted with agents approved for other indications or under clinical development. The need to generate increasing amounts of genomic information should prompt health-care providers to be mindful of the amounts of tissue needed for these assays when planning diagnostic procedures. In this review, we summarize oncogenic drivers in NSCLC that can be currently detected, highlight their potential therapeutic implications, and discuss practical considerations for successful application of tumor genotyping in clinical decision making.Keywords: lung cancer; cancer genomics; molecular targeted therapy Lung cancer remains the leading cause of cancer-related mortality in the United States and worldwide. Approximately 85% of patients are diagnosed with non-small cell lung cancer (NSCLC), and most present with advanced disease that is not amenable to curative therapy. For these patients, cytotoxic chemotherapy offers modest prolongation in survival. Over the past 2 decades, modifications of chemotherapy combinations, the addition of monoclonal antibodies, including bevacizumab and cetuximab, and the incorporation of histologic subtype into treatment decisions have added incrementally to the survival of patients with advanced NSCLC. However, therapeutic outcomes appear to have reached a plateau, with response rates of 20 to 35% and median survival of 8 to 12 months (1-3). Recently, clinical and laboratory research have led to a better understanding of the molecular pathogenesis that causes lung cancer. The ongoing research of patients with NSCLC and their tumors has demonstrated that NSCLC can be further defined at the molecular level by the identification and characterization of oncogenic drivers that occur in genes critical to cellular proliferation and survival, leading to aberrant activation of signaling proteins that induce sustained growth of the lung cancer cells. These advances in the molecular pathogenesis of NSCLC have prompted investigators to systematically characterize lung cancers for these oncogenic drivers and treat with appropriate targeted therapies. A cohort of patients can now be prospectively identified who have significantly improved outcomes with such therapies, with median survival in excess of 2 years, necessitating the routine identification of these genomically defined patient subsets. In this perspective, we review oncogenic ...

show abstract

Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu

Cited by 246 publications

References 19 publications

Extracellular Domain Mutation of ErbB2 Status in Japanese Lung Cancer Patients

Extracellular Domain Mutation of ErbB2 Status in Japanese Lung Cancer Patients

Review of the current targeted therapies for non-small-cell lung cancer

The Impact of Genomic Changes on Treatment of Lung Cancer

Contact Info

Product

Resources

About