Investigating the genomic alteration improved the clinical outcome of aged patients with lung carcinoma.

BACKGROUND: Lung carcinoma is a common geriatric disease. The development of genotype-targeted therapies greatly improved the management of lung carcinoma. However, the treatment for old patients can be more complex than that for young individuals. RESULTS: To investigate the benefits of genetic detection for older patients with lung carcinoma, we explored the genomic profiling of 258 patients with more than 55 years using a targeted next generation sequencing, and some of these patients were treated with targeted therapies based on the results of genomic detection. KRAS codon 61 mutations were found in 15.2% KRAS-mutated patients, which tend to be co-existing with other classical activating mutations other than codons 12/13. Acquired EGFR C797S mutations were identified in 2 cases and ERBB2 amplification was identified in 1 case. All these 3 cases developed resistance to EGFR tyrosine kinase inhibitors and showed expected results of their followed therapies. The median progression-free survival and median overall survival of patients treated with molecular targeted therapies were better than those of patients treated with chemoradiotherapy alone. CONCLUSIONS: Our findings revealed the specific genomic profiles of patients older than 55 years with lung carcinoma and suggested that these old patients have been benefit from the genetic detection, which helped identify druggable mutations and distinguish resistance mechanisms.

Combination therapy with afatinib and bevacizumab in an EGFR-mutated non-small cell lung cancer patient with acquired ERBB2 amplification: A case report.

INTRODUCTION: Acquired resistance to reversible EGFR tyrosine kinase inhibitors remains a significant obstacle, and acquired ERBB2 amplification is the most common "bypass" mechanism. For patients with sensitizing EGFR mutation who experience resistance via ERBB2 amplification, no targeted drug has been demonstrated to be effective. PATIENT CONCERNS: A 56-year-old female nonsmoker suffered from left leg paralysis and low back pain. Imaging examination revealed a mass in the anterior segment of the right upper lobe lung and possible multiple metastases in the right hilar, mediastinal lymph nodes, bone metastases, and soft tissue invasion. DIAGNOSIS: Transbronchial lung biopsy revealed a moderately differentiated adenocarcinoma (cT4N2M1c, stage IV). An EGFR exon 19 deletion was identified using amplification refractory mutation system. INTERVENTIONS: After the patient was treated with gefitinib initiation (250 mg/d) for 15 months, the tumor progressed with ERBB2 amplification revealed by next-generation sequencing test. Then, the patient was started on afatinib (40 mg/d) plus bevacizumab (7.5 mg/kg every 3 weeks). OUTCOMES: The combination therapy of afatinib and bevacizumab in this patient was effective with some slight side effects. Computed tomography scans showed the tumor shrinkage and the pleural effusion disappeared in the right lung. The overall survival was 23.5 months. CONCLUSION: To date, there is no targeted therapy approved and demonstrated to be effective for non-small cell lung cancer patients with EGFR sensitizing mutations, and ERBB2 amplification. The effectiveness of combination therapy with afatinib and bevacizumab may provide a new therapeutic option for these patients.