Genomic signatures define three subtypes of EGFR-mutant stage II–III non-small-cell lung cancer with distinct adjuvant therapy outcomes

Liu, Siyang; Bao, Hua; Wang, Qun; Mao, Weimin; Chen, Yedan; Tong, Xiaoling; Xu, Songtao; Wu, Lin; Wei, Yucheng; Liu, Yong‐Yu; Chen, Chun; Cheng, Ying; Yin, Rong; Yang, Fan; Ren, Shengxiang; Li, Xiaofei; Li, Jian; Huang, Cheng; Liu, Zhidong; Xu, Shun; Chen, Ke-Neng; Xu, Shidong; Liu, Lunxu; Yu, Ping; Wang, Buhai; Ma, Hu; Yan, Hong‐Hong; Dong, Song; Zhang, Xuchao; Su, Jian; Yang, Jing; Yang, Xue‐Ning; Zhou, Qing; Wu, Xue; Shao, Yang; Zhong, Wen‐Zhao; Wu, Yi‐Long

doi:10.1038/s41467-021-26806-7

Cited by 55 publications

(48 citation statements)

References 63 publications

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“…A comprehensive tumor genomic analysis of resected EGFR -mutant NSCLC (mainly LUAD) specimens suggested that additional predictive biomarkers may be useful to guide personalized adjuvant therapy within patients with resected EGFR -mutant NSCLC. 53 , 54 …”

Section: Discussionmentioning

confidence: 99%

Real-World Survival Outcomes Based on EGFR Mutation Status in Chinese Patients With Lung Adenocarcinoma After Complete Resection: Results From the ICAN Study

Yang

Yan

Wang

et al. 2022

JTO Clinical and Research Reports

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Introduction The adjuvant treatment of patients with resected lung adenocarcinoma (LUAD) remains unstandardized. We analyzed the survival outcomes of these patients based on EGFR mutation status and adjuvant chemotherapy treatment. Methods This noninterventional real-world study (ICAN) enrolled Chinese patients with resected stages I to III LUAD from April 8, 2010, to December 31, 2010. Tumor EGFR mutation status and 3-year disease-free survival (DFS) were determined. The extension phase provided long-term follow-up with overall survival (OS) as the primary end point. Secondary end points included DFS and prognostic factors of survival. Survival outcomes based on adjuvant chemotherapy treatment, EGFR mutation status, and postoperative stage were analyzed post hoc. Results Among 568 patients in the ICAN cohort, 472 continued to the extension phase and remained eligible. The 3-year DFS rate was 58.8%. In the extension cohort, 260 patients (55.1%) had EGFR -mutant disease and 207 (43.9%) received adjuvant chemotherapy. At a median follow-up of 109.0 (95% confidence interval [CI]: 106.6–111.4) months, median OS and DFS were 103.3 (95% CI: 101.7–104.9) and 67.4 (95% CI: 49.7–85.2) months, respectively. The 5-year OS and DFS rates were 68.9% (95% CI: 64.3–73.6) and 52.9% (95% CI: 48.2–57.7), respectively. EGFR wild-type disease was a significant independent predictor of worse OS (HR = 1.24, 95% CI: 1.07–1.44, p = 0.004) based on the Cox regression analysis of common factors. Post hoc subgroup analysis revealed that survival outcomes were not significantly different with adjuvant chemotherapy regardless of EGFR mutation status across all postoperative stages. Conclusions EGFR mutations are common in operable LUAD, and recurrence and mortality after resection were considerable. Adjuvant chemotherapy did not improve survival outcomes, regardless of EGFR mutation status and postoperative stage.

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Section: Discussionmentioning

confidence: 99%

Real-World Survival Outcomes Based on EGFR Mutation Status in Chinese Patients With Lung Adenocarcinoma After Complete Resection: Results From the ICAN Study

Yang

Yan

Wang

et al. 2022

JTO Clinical and Research Reports

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“…This evidence, together with the fact that TP53 mutations are more frequent in EGFR -mutated patients, suggest that some of these oncogene-addicted tumors could possess an underlying biology and molecular mechanisms based on two main biomarkers to guide cancer progression [ 5 , 108 ]. On the other hand, in an attempt to find predictive biomarkers for a neo-adjuvant therapy for stage II–III EGFR -mutated NSCLC, exon 4/5 TP53 missense mutations have been found to be a stratification factor for OS and treatment [ 109 ]; another study based on the IALT trial case series, found that TP53 mutations play a role in predicting the efficacy of adjuvant platinum-based chemotherapy [ 110 ]. In the next paragraph, we discuss the emerging role of TP53 in EGFR -mutated patients, both in terms of prognostic impact and resistance to targeted therapy.…”

Section: Tp53 Mutations In Nsclcmentioning

confidence: 99%

The Role of TP53 Mutations in EGFR-Mutated Non-Small-Cell Lung Cancer: Clinical Significance and Implications for Therapy

Canale

Andrikou

Priano

et al. 2022

Cancers

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Non-Small-Cell Lung Cancer (NSCLC) is the primary cause of cancer-related death worldwide. Oncogene-addicted patients usually benefit from targeted therapy, but primary and acquired resistance mechanisms inevitably occur. Tumor protein 53 (TP53) gene is the most frequently mutated gene in cancer, including NSCLC. TP53 mutations are able to induce carcinogenesis, tumor development and resistance to therapy, influencing patient prognosis and responsiveness to therapy. TP53 mutants present in different forms, suggesting that different gene alterations confer specific acquired protein functions. In recent years, many associations between different TP53 mutations and responses to Epidermal Growth Factor Receptor (EGFR) targeted therapy in NSCLC patients have been found. In this review, we discuss the current landscape concerning the role of TP53 mutants to guide primary and acquired resistance to Tyrosine-Kinase Inhibitors (TKIs) EGFR-directed, investigating the possible mechanisms of TP53 mutants within the cellular compartments. We also discuss the role of the TP53 mutations in predicting the response to targeted therapy with EGFR-TKIs, as a possible biomarker to guide patient stratification for treatment.

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“…Precision therapy for non-small cell lung cancer (NSCLC) based on genetic alterations greatly changed clinical practice (1,2). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have become the standard of care for advanced NSCLC (3)(4)(5)(6). The ADJUVANT-CTONG 1104 trial (Clinicaltrials.gov NCT01405079) demonstrated that the first-generation EGFR-TKI adjuvant gefitinib improves disease-free survival (DFS) from 19.8 months to 30.8 months for resected EGFR mutant NSCLC with N1/N2 metastasis; the subsequent ADAURA trial, the first international study with the third-generation EGFR-TKI osimertinib, reported positive outcomes for adjuvant TKIs in patients with EGFR mutations as well (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Predictive value of TCR Vβ-Jβ profile for adjuvant gefitinib in EGFR mutant NSCLC from ADJUVANT-CTONG 1104 trial

Chen¹,

Liu²,

Chen³

et al. 2022

JCI Insight

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Herein, we characterize the landscape and prognostic significance of the T cell receptor (TCR) repertoire of early-stage non–small cell lung cancer (NSCLC) for patients with an epidermal growth factor receptor ( EGFR ) mutation. β Chain TCR sequencing was used to characterize the TCR repertoires of paraffin-preserved pretreatment tumor and tumor-adjacent tissues from 57 and 44 patients with stage II/III NSCLC with an EGFR mutation treated with gefitinib or chemotherapy in the ADJUVANT-CTONG 1104 trial. The TCR diversity was significantly decreased in patients with an EGFR mutation, and patients with high TCR diversity had a favorable overall survival (OS). A total of 10 TCR Vβ-Jβ rearrangements were significantly associated with OS. Patients with a higher frequency of Vβ5-6Jβ2-1, Vβ20-1Jβ2-1, Vβ24-1Jβ2-1, and Vβ29-1Jβ2-7 had significantly longer OS. Weighted combinations of the 4 TCRs were significantly associated with OS and disease-free survival (DFS) of patients, which could further stratify the high and low TCR diversity groups. Importantly, Vβ5-6Jβ2-1, Vβ20-1Jβ2-1, and Vβ24-1Jβ2-1 had a significant relationship with gefitinib treatment, while Vβ29-1Jβ2-7 was associated with chemotherapy. Four TCR Vβ-Jβ rearrangements related to favorable OS and DFS for adjuvant gefitinib and chemotherapy in patients with an EGFR mutation with stage II/III NSCLC; this may provide a novel perspective for the adjuvant setting for resectable NSCLC.

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Genomic signatures define three subtypes of EGFR-mutant stage II–III non-small-cell lung cancer with distinct adjuvant therapy outcomes

Cited by 55 publications

References 63 publications

Real-World Survival Outcomes Based on EGFR Mutation Status in Chinese Patients With Lung Adenocarcinoma After Complete Resection: Results From the ICAN Study

Real-World Survival Outcomes Based on EGFR Mutation Status in Chinese Patients With Lung Adenocarcinoma After Complete Resection: Results From the ICAN Study

The Role of TP53 Mutations in EGFR-Mutated Non-Small-Cell Lung Cancer: Clinical Significance and Implications for Therapy

Predictive value of TCR Vβ-Jβ profile for adjuvant gefitinib in EGFR mutant NSCLC from ADJUVANT-CTONG 1104 trial

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