First report of furmonertinib as a first-line treatment in advanced lung adenocarcinoma patients harboring EGFR exon 20 insertion mutations after the kinase domain αC-helix: Two case reports and a literature review.

RATIONALE: Many studies have shown that first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors are less effective in patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations. The efficacy of third-generation epidermal growth factor receptor tyrosine kinase inhibitors is still under investigation. Although new targeted tyrosine kinase inhibitors and monoclonal antibody-based agents have made significant advances in the treatment of epidermal growth factor receptor exon 20 insertion (EGFR ex20ins) mutation, the efficacy of these novel agents is not quite satisfactory. Platinum- and pemetrexed-based chemotherapy remains the standard first-line treatment for patients harboring EGFR ex20ins mutation. PATIENT CONCERNS: We report for the first time 2 Chinese patients diagnosed with advanced lung adenocarcinoma with EGFR ex20ins mutations after analysis of the αC-helix sequence by next-generation sequencing. Both patients were treated with furmonertinib as the first-line therapy. INTERVENTIONS: The first case included a 38-year-old female who had an EGFR ex20ins mutation (p.S768_D770dupSVD). After 1 month of treatment with furmonertinib, her symptoms of pain and cough were significantly alleviated. She achieved a partial response according to response evaluation criteria in solid tumors.[1] The final progression-free survival was 8.13 months. The second case included a 40-year-old male who had an EGFR ex20ins mutation (p.N771_P772insVal). He had a good response to furmonertinib and exhibited stable disease according to response evaluation criteria in solid tumors with a progression-free survival of 10.90 months. OUTCOMES: Both patients experienced significant improvement in symptoms and prolonged survival after furmonertinib was used as first-line treatment. Side effects were limited but manageable. CONCLUSION: The present study indicates that furmonertinib may be a first-line treatment option for patients with non-small cell lung cancer harboring EGFR ex20ins mutation.

Case Report: A good response to furmonertinib second-line treatment of an advanced lung adenocarcinoma patient with a rare EGFR exon 20 N771_P772insH mutation: A case report and literature review.

Background: Lung adenocarcinoma with the classical EGFR 19 deletion and exon 21 L858R point mutations has exhibited good responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. However, the sensitivity of uncommon EGFR exon 20 insertion mutation to third-generation EGFR-TKIs has not been determined. Although emerging targeted therapies for EGFR exon 20 insertion mutation have been reported in recent years, such patients still have a poorer prognosis than those with typical or wild-type EGFR mutations. Case summary: Here, we report the case of a 57-year-old man with advanced non-small cell lung cancer (NSCLC) with a rare EGFR exon 20 N771_P772insH mutation. The patient was treated with furmonertinib as second-line therapy. Although his pleural effusion was more than before that during treatment, various examination results showed that the pleural effusion was closely related to hypoproteinemia; thus, local progression was not considered. His cough was significantly alleviated, and the dose was well tolerated. The patient was evaluated for a remarkable progression-free survival (PFS) of 10.0 months, a duration of response (DOR) of 8.0 months, and an overall survival (OS) of 22.0 months, which had not previously been achieved. Conclusion: The present study indicated that furmonertinib might be a good treatment option for first-line progressive NSCLC patients with EGFR exon 20 insertion mutation.

Case report: sequential use of almonertinib based on the EGFR exon 20 insertion mutation achieves long-term control for advanced non-small cell lung cancer patients.

Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) play a dominant role in the treatment of non-small cell lung cancer (NSCLC); however, to date, targeted treatment options have not been identified for patients with EGFR exon 20 insertion (ex20ins) mutations. Almonertinib, as the third generation EGFR-TKI, can irreversibly bind to EGFR ATP binding region and has a favorable therapeutic effect in EGFR + multiple targets inhibition. Almonertinib is suitable for the treatment of NSCLC patients with disease progression and T790M drug resistance mutation positive after other EGFR-TKI treatment. Case Description: We report the case of a female patient with NSCLC with an EGFR ex20ins mutation (p.Ala767_Val769dup) identified by next-generation sequencing (NGS). The patient received systemic chemotherapy after surgical resection of the lesion. After the progression of first-line chemotherapy, the patient received sequential targeted therapy with afatinib and poziotinib, achieving progression-free survival (PFS) of 3.2 and 10.4 months, respectively. After the progression, we chose almonertinib when the patient refused to re-chemotherapy. Under the treatment of almonertinib, the PFS time of the patient reached 14 months. Conclusions: Almonertinib had the most substantial effect, and its use has not been previously reported for NSCLC patients with EGFR ex20ins mutations. The successful application of almonertinib reported here indicates that is a potential new treatment regimen for patients with EGFR ex20ins mutations.

Genetic Alteration and Their Significance on Clinical Events in Small Cell Lung Cancer.

Introduction: Small cell lung cancer (SCLC), an aggressive subtype of lung cancer characterized by the development of neuroendocrine tumors, is prone to distant metastasis, resistant to platinum-based drugs and has a poor prognosis. The development of next-generation sequencing technology (NGS) has led to the identification of many genetic alterations in SCLC. Few druggable targeted molecules can be used in clinical practice. Currently, NGS is widely employed in routine clinical practice of non-small cell lung cancer to assist in therapeutic options and prognosis evaluation. This study aims to investigate genes involved in small cell lung cancer (SCLC), their occurrence and their significance in clinical events. Methods: Tumor tissue specimens from 18 Chinese SCLC patients were collected through a 520 cancer-related genes panel for next-generation sequencing. First, the association between sequence results and clinical outcomes was examined. Subsequently, data on clinical pathology and sequencing results were analyzed. Results: The Kaplan-Meier curve displayed a significant reduction in PFS for SCLC patients with LRP1B or MAP3K13 mutations. Overall survival (OS) of SCLC patients with MSH6 mutation was significantly higher than those with SPEN mutation. Conclusion: Next-generation sequencing demonstrates that the genetic landscape of SCLC. Mutation status of LRP1B, MAP3K13, MSH6 and SPEN has prognostic significance, which might be potential therapeutic targets. We found possible genes and related signaling pathways that affect metastasis. These results can improve our understanding of the mutation characteristics of SCLC and identify potential biomarkers to guide targeted therapies.

Evolution of Lung Cancer in the Context of Immunotherapy.

Immunotherapy, as a novel treatment, has brought new hope to many patients with cancer, including patients with lung cancer. However, the overall cure rate and survival rate of lung cancer are still not satisfactory. The process of evolution has improved the ability of tumors to adapt to immunotherapy, which induces drug resistance. Many studies have focused on immunoresistance and achieved meaningful results. Therefore, it is necessary to have an in-depth understanding of the current research progress in immunoresistance, which will help to achieve good clinical results more efficiently.

Upregulation of IBSP Expression Predicts Poor Prognosis in Patients With Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC), which is characterized by invasiveness and poor prognosis, is the sixth most common leading cause of cancer-related death worldwide. Despite advances in multimodality therapy, ESCC mortality remains high, and an understanding of the molecular changes that lead to ESCC development and progression remains limited. In the present study, Integrin Binding Sialoprotein (IBSP) upregulation was found in 182 of 269 (67.7%) primary ESCC cells at the mRNA level by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, IHC staining further demonstrated that IBSP was upregulated in ESCC patients and IBSP protein upregulation was significantly related to the lymph node metastasis (P = 0.017), clinicopathologic stage (P = 0.001) and poor disease survival (P = 0.002). Moreover, functional studies illustrated that the IBSP gene can promote the proliferation and metastasis of ESCC cells. Furthermore, IBSP was found to regulate epithelial-mesenchymal transition (EMT), which promotes tumor cell metastasis. In conclusion, our study suggests that IBSP may be a valuable prognostic marker for ESCC patients.