&lt;p&gt;Third-Generation TKI Resistance Due to SCLC Transformation: A Case Report and Brief Review&lt;/p&gt;

Chen, Shen; He, Yayi; Liu, Juan; Chen, Xiaoxia; Yu, Jia; Li, Wei; Chen, Bin; Sun, Chengtao; Zhou, Caicun

doi:10.2147/ott.s228301

Cited by 15 publications

(15 citation statements)

References 22 publications

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“…[5][6][7][8] However, about 40% of patients with SCLC remain insensitive to chemotherapy. [9][10][11] Recently, immunotherapy showed certain advantages in the treatment of SCLC. 9 12-15 Showing improvements in patient prognosis, atezolizumab, one of programmed death ligands-1 (PD-L1) inhibitors, was approved by the Food and Drug Administration in the treatment of ED-SCLC.…”

Section: Introductionmentioning

confidence: 99%

Galectin-9-based immune risk score model helps to predict relapse in stage I–III small cell lung cancer

Chen

Zhang

et al. 2020

J Immunother Cancer

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BackgroundFor small cell lung cancer (SCLC) therapy, immunotherapy might have unique advantages to some extent. Galectin-9 (Gal-9) plays an important role in antitumor immunity, while little is known of its function in SCLC.Materials and methodsBy mean of immunohistochemistry (IHC), we tested the expression level of Gal-9 and other immune markers on both tumor cells and tumor-infiltrating lymphocytes (TILs) in 102 surgical-resected early stage SCLC clinical samples. On the basis of statistical analysis and machine learning results, the Gal-9-based immune risk score model was constructed and its predictive performance was evaluated. Then, we thoroughly explored the effects of Gal-9 and immune risk score on SCLC immune microenvironment and immune infiltration in different cohorts and platforms.ResultsIn the SCLC cohort for IHC, the expression level of Gal-9 on TILs was statistically correlated with the levels of program death-1 (p=0.001), program death-ligand 1 (PD-L1) (p<0.001), CD3 (p<0.001), CD4 (p<0.001), CD8 (p<0.001), and FOXP3 (p=0.047). High Gal-9 protein expression on TILs indicated better recurrence-free survival (30.4 months, 95% CI: 23.7–37.1 vs 39.4 months, 95% CI: 31.6–47.3, p=0.009). The immune risk score model which consisted of Gal-9 on TILs, CD4, and PD-L1 on TILs was established and validated so as to differentiate high-risk or low-risk patients with SCLC. The prognostic predictive performance of immune risk score model was better than single immune biomarker (area under the curve 0.671 vs 0.621–0.644). High Gal-9-related enrichment pathways in SCLC were enriched in immune system diseases and rheumatic disease. Furthermore, we found that patients with SCLC with low immune risk score presented higher fractions of activated memory CD4 T cells than patients with high immune risk score (p=0.048).ConclusionsGal-9 is markedly related to tumor-immune microenvironment and immune infiltration in SCLC. This study emphasized the predictive value and promising clinical applications of Gal-9 in stage I–III SCLC.

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Section: Introductionmentioning

confidence: 99%

Galectin-9-based immune risk score model helps to predict relapse in stage I–III small cell lung cancer

Chen

Zhang

et al. 2020

J Immunother Cancer

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“…After developing a resistance to EGFR-TKI, the patient was treated with a variety of regimens, including etoposide combined with carboplatin (EC), irinotecan combined with oxaliplatin (IO), Abraxane, and Apatinib. However, quick progression was observed (15). Lai et al presented 2 cases in which the patients diagnoses transformed to SCLC after 1st-and 3rd-generation EGFR-TKI resistance and response to EP regimen and erlotinib; these patients passed away due to acute pulmonary embolism or severe pneumonia (16).…”

Section: Discussionmentioning

confidence: 99%

Case report: EGFR-mutant lung adenocarcinoma with the TP53 and RB1 mutations showed resistance to TKI therapy

Lu¹,

Li²,

Zhu³

et al. 2021

Ann Palliat Med

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Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a standard treatment for patients with advanced non-small-cell lung cancer (NSCLC) harboring classic EGFR mutations. However, resistance to TKIs remains a major clinical challenge. The transformation from adenocarcinoma to small-cell lung cancer (SCLC) is a rare resistance mechanism to EGFR-TKIs. In this article, we report on 2 lung adenocarcinoma patients with EGFR mutations who developed EGFR-TKI resistance. In case one, the patient was initially diagnosed as lung adenocarcinoma with EGFR L858R, RB1 R445*, and TP53 Y205C mutations. EGFR-TKI failed to bring satisfactory curative effect with the emergence of EGFR T790M mutation and MET amplification and finally passed away. In case two, the patient was diagnosed with lung cancer harboring EGFR L747 and TP53 R342* mutations, and EGFR-TKIs brought a progression-free survival for nine month. However, EGFR-TKI resistance was acquired, and adenocarcinoma transformed into a complex of neuroendocrine carcinoma, SCLC, and lung adenocarcinoma, with the emergence of the EGFR L747, TP53 R342*, and RB1 mutations. Follow-up treatments failed to prevent tumor progression, and the patient died These 2 cases expand our understanding of EGFR-TKI resistance, SCLC transformation, and highlight the importance of histopathology and molecular characteristics for therapeutic strategies for transformed SCLC patients.

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“…Lung adenocarcinoma (LADC) patients with epidermal growth factor receptor ( EGFR ) mutations will inevitably develop resistance during treatment with EGFR tyrosine kinase inhibitors (TKIs). Although almost 60% of acquired resistance to first‐ or second‐generation EGFR‐TKIs have been reported to result from secondary T790M mutation, 1 transformation to small cell lung cancer (SCLC) also accounts for about 3%–14% resistance to first‐ or second‐generation EGFR‐TKIs 1,2 and is seen in resistance to third‐generation EGFR‐TKIs as well 3,4 …”

Section: Introductionmentioning

confidence: 99%

“…The optimal treatment choices for LADC patients who develop SCLC transformation remain unclear. Some cases have been reported to receive chemotherapy for SCLC alone after transformation, 3,4,9–12 while other cases have received a combination of chemotherapy and EGFR‐TKIs 4,9,13 . The response status and progression‐free survival (PFS) varied from case to case.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of treatment modes and clinical outcomes of small cell lung cancer transformed from epidermal growth factor receptor mutant lung adenocarcinoma

et al. 2021

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Background Transformation to small cell lung cancer (SCLC) is a resistance mechanism of epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma (LADC) patients treated with EGFR tyrosine kinase inhibitors (TKIs). Here, we describe the clinical characteristics and prognosis of these patients and explore the treatment modes after transformation. Methods EGFR‐mutant LADC patients with SCLC transformation were retrospectively included in the study. Demographic and clinical data were collected. Survival outcomes and corresponding influential factors were analyzed. Results Twenty‐nine patients were included in the study. The median progression‐free survival (PFS) of patients who received first‐line EGFR‐TKIs was 13.1 months. The median time to SCLC transformation was 27.5 months. After transformation, the objective response rates of patients who received first‐line chemotherapy with or without EGFR‐TKIs were 43.8% and 37.5%, respectively. The median PFS of patients reveiving chemotherapy with EGFR‐TKIs was significantly longer than that of patients receiving chemotherapy without EGFR‐TKIs (5.2 vs. 3.0 months; HR, 0.19; 95% CI: 0.05–0.72; p = 0.014). However, there was no significant difference in median overall survival (OS) between patients who received chemotherapy with or without EGFR‐TKIs (14.8 vs. 13.0 months; p = 0.474). In the multivariate Cox proportional hazards regression analysis, both anti‐angiogenic treatment (HR, 0.04; 95% CI: 0.01–0.29; p = 0.001) and local radiotherapy (HR, 0.28; 95% CI: 0.08–0.97; p = 0.044) were significantly associated with better patient OS after transformation. Conclusions Compared with chemotherapy alone, the combination of chemotherapy and EGFR‐TKIs as first‐line treatment after SCLC transformation can benefit patients in PFS but not in OS. However, anti‐angiogenic therapies and local radiotherapy can significantly prolong OS after transformation.

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<p>Third-Generation TKI Resistance Due to SCLC Transformation: A Case Report and Brief Review</p>

Cited by 15 publications

References 22 publications

Galectin-9-based immune risk score model helps to predict relapse in stage I–III small cell lung cancer

Galectin-9-based immune risk score model helps to predict relapse in stage I–III small cell lung cancer

Case report: EGFR-mutant lung adenocarcinoma with the TP53 and RB1 mutations showed resistance to TKI therapy

Comprehensive analysis of treatment modes and clinical outcomes of small cell lung cancer transformed from epidermal growth factor receptor mutant lung adenocarcinoma

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