Genomic alterations and clinical outcomes in patients with lung adenocarcinoma with transformation to small cell lung cancer after treatment with EGFR tyrosine kinase inhibitors: A multicenter retrospective study

Wang, Wenxian; Xu, C.; Chen, Huafei; Jia, Jinhao; Wang, Liping; Feng, Huijing; Wang, Hong; Song, Zhengbo; Yang, Nong; Zhang, Yongchang

doi:10.1016/j.lungcan.2021.03.006

Cited by 47 publications

(40 citation statements)

References 24 publications

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“…Even though the efficacy of anti‐angiogenic therapies for primary SCLC patients is controversial, 16–21 a previous study has suggested that anlotinib may be a therapeutic option for EGFR ‐mutant patients transforming to SCLC, with an ORR of 66.7% and a median PFS of 6.2 months 15 . Our study further identified the value of anti‐angiogenic treatment for these patients by revealing that patients treated with anti‐angiogenic therapies after transformation could obtain OS benefit.…”

Section: Discussionsupporting

confidence: 53%

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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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Section: Discussionsupporting

confidence: 53%

“…The response status and progression‐free survival (PFS) varied from case to case. Two studies reported that the objective response rate (ORR) to platinum‐etoposide therapy was nearly 50% and the median PFS was about 3.5 months 14,15 . However, whether EGFR‐TKIs should be continued or not is controversial.…”

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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“…Small cell transformation has been widely reported as a mechanism of resistance in patients with EGFR ‐mutant or ALK‐rearranged NSCLC 4–7 . However, the frequency of small cell transformation has been reported to be very low after acquired resistance to crizotinib or lorlatinib in patients with ROS1 positive NSCLC 8 .…”

Section: Discussionmentioning

confidence: 99%

“…Data regarding resistance mechanisms in the remaining patients are limited. Small cell transformation has been identified as an important resistance mechanism in 3%–10% of patients with epidermal growth factor receptor (EGFR)‐mutant or anaplastic lymphoma kinase (ALK)‐rearranged NSCLC after receiving EGFR‐ TKIs or ALK‐TKIs 4–7 . It is associated with poor prognosis due to its aggressiveness and poor response to systemic chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…Small cell transformation has been identified as an important resistance mechanism in 3%–10% of patients with epidermal growth factor receptor (EGFR)‐mutant or anaplastic lymphoma kinase (ALK)‐rearranged NSCLC after receiving EGFR‐ TKIs or ALK‐TKIs. 4 , 5 , 6 , 7 It is associated with poor prognosis due to its aggressiveness and poor response to systemic chemotherapy. However, reports regarding small cell transformation as a resistance mechanism in ROS1‐rearranged NSCLC patients and genomic alterations after histological transformation remain limited.…”

Section: Introductionmentioning

confidence: 99%

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Small cell transformation in crizotinib‐resistant ROS1‐rearranged non‐small cell lung cancer with retention of ROS1 fusion: A case report

Hsu

et al. 2021

Thoracic Cancer

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C‐ros oncogene 1 receptor tyrosine kinase (ROS1) rearrangement has been detected in patients with advanced non‐small cell lung cancer (NSCLC). Although ROS1 tyrosine kinase inhibitors (TKIs) provide a survival benefit for patients with ROS1‐rearranged advanced NSCLC, subsequent therapy remains limited. Small cell transformation is an important mechanism of drug resistance in epidermal growth factor receptor‐mutant NSCLC. However, its significance in mediating ROS1 resistance has not been determined yet. Here, we present the case of a 63‐year‐old man with ROS1‐rearranged advanced NSCLC who had disease progression with small cell transformation of the mediastinal lymph node after 8 months of treatment with crizotinib. More importantly, fluorescence in situ hybridization of post‐progression tumor biopsy demonstrated retention of ROS1 rearrangement. Tissue biopsy remains indispensable for patients who acquire resistance to ROS1 TKIs.

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Genotyping of RB1 status identifies two distinct subtypes in EGFR‐mutant lung cancers with SCLC transformation

Huang,

Zhang,

Zhang

et al. 2024

Clinical & Translational Med

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Dear Editor, In this study, we investigate the significant yet underexplored clinical and molecular heterogeneity in epidermal growth factor receptor (EGFR)-mutant lung cancers transformed into small cell lung cancer (SCLC). Our work addresses a crucial unmet need in understanding the molecular underpinnings of this transformation and introduces a novel predictive model for assessing the transformation hazards in high-risk patients.Up to 14% of EGFR-mutant non-SCLC (NSCLC) patients experience SCLC transformation (T-SCLC) under the selective pressure of EGFR tyrosine kinase inhibitors (TKIs), 1 and the significant heterogeneity within this population is increasingly recognised, including response to EGFR-TKIs, time to transformation, survival and genetic profile. 2-4 However, this patient population is generally treated as a homogeneous entity, yet their posttransformation prognosis is often worse than that of de novo SCLC. 4,5 Hence, it is rational to define EGFRmutant lung cancer with T-SCLC into distinct subtypes, potentially uncovering new therapeutic targets and vulnerabilities.We conducted a retrospective analysis of 1436 EGFRmutant NSCLC patients at the Guangdong Lung Cancer Institute between January 2017 and December 2021. This cohort included 63 patients who underwent T-SCLC and 97 patients who harboured concomitant RB1 and TP53 alterations along with EGFR mutation (Supporting Information Figure S1). Furthermore, T-SCLC patients were stratified into two subgroups based on pre-transformation RB1 status: the EGFR-mutant/RB1-wild subgroup (n = 21) and the EGFR/RB1-mutant subgroup (n = 34). Additionally, EGFR/RB1/TP53-mutant patients were categorised into the transformed subgroup (n = 34) and the untransformed subgroup (n = 27). Notably, the transformed subgroup completely overlapped with the EGFR/RB1-mutant subgroup, as all the patients in the EGFR/RB1-mutant subgroup harboured TP53 mutations simultaneously (Supporting Information: Methods).

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Genomic alterations and clinical outcomes in patients with lung adenocarcinoma with transformation to small cell lung cancer after treatment with EGFR tyrosine kinase inhibitors: A multicenter retrospective study

Cited by 47 publications

References 24 publications

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

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

Small cell transformation in crizotinib‐resistant ROS1‐rearranged non‐small cell lung cancer with retention of ROS1 fusion: A case report

Genotyping of RB1 status identifies two distinct subtypes in EGFR‐mutant lung cancers with SCLC transformation

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