Novel targeted agents for the treatment of lung cancer in China

Liu, Si Yang; Mok, Tony; Wu, Yi‐Long

doi:10.1002/cncr.29522

Cited by 11 publications

(14 citation statements)

References 53 publications

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“…In this NGS‐based study of Chinese patients with NSCLC, a comprehensive profile of genomic alterations was constructed. In gene mutations of EGFR , KRAS , and ALK , Chinese patients with NSCLC were different from the Western population, as the former had a much higher frequency (47.6% vs. 20.0%) of EGFR mutations and ALK rearrangements (7.8% vs. 4.1%) but a significantly lower frequency (10.8% vs. 32.0%) of KRAS mutation than the latter , which was consistent with previous reports . Nearly three quarters of Chinese patients with NSCLC harbored at least one druggable genomic alteration of driver genes recommended by the NCCN guideline, revealing the different clinical characteristics of Chinese patients.…”

Section: Discussionsupporting

confidence: 87%

Genomic Signature of Driver Genes Identified by Target Next-Generation Sequencing in Chinese Non-Small Cell Lung Cancer

Dai

Wang

et al. 2019

The Oncologist

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Background Non‐small cell lung cancer (NSCLC) is one of the most common human malignancies and the leading cause of cancer‐related death. Over the past few decades, genomic alterations of cancer driver genes have been identified in NSCLC, and molecular testing and targeted therapies have become standard care for lung cancer patients. Here we studied the unique genomic profile of driver genes in Chinese patients with NSCLC by next‐generation sequencing (NGS) assay. Materials and Methods A total of 1,200 Chinese patients with NSCLC were enrolled in this study. The median age was 60 years (range: 26–89), and 83% cases were adenocarcinoma. NGS‐based genomic profiling of major lung cancer‐related genes was performed on formalin‐fixed paraffin‐embedded tumor samples and matched blood. Results Approximately 73.9% of patients with NSCLC harbored at least one actionable alteration recommended by the National Comprehensive Cancer Network guideline, including epidermal growth factor receptor (EGFR), ALK, ERBB2, MET, BRAF, RET, and ROS1. Twenty‐seven patients (2.2%) harbored inherited germline mutations of cancer susceptibility genes. The frequencies of EGFR genomic alterations (both mutations and amplification) and ALK rearrangement were identified as 50.1% and 7.8% in Chinese NSCLC populations, respectively, and significantly higher than the Western population. Fifty‐six distinct uncommon EGFR mutations other than L858R, exon19del, exon20ins, or T790M were identified in 18.9% of patients with EGFR‐mutant NSCLC. About 7.4% of patients harbored both sensitizing and uncommon mutations, and 11.6% of patients harbored only uncommon EGFR mutations. The uncommon EGFR mutations more frequently combined with the genomic alterations of ALK, CDKN2A, NTRK3, TSC2, and KRAS. In patients <40 years of age, the ALK‐positive percentage was up to 28.2%. Moreover, 3.2% of ALK‐positive patients harbored multi ALK rearrangements, and seven new partner genes were identified. Conclusion More unique features of cancer driver genes in Chinese NSCLC were identified by next‐generation sequencing. These findings highlighted that NGS technology is more feasible and necessary than other molecular testing methods, and suggested that the special strategies are needed for drug development and targeted therapy for Chinese patients with NSCLC. Implications for Practice Molecular targeted therapy is now the standard first‐line treatment for patients with advanced non‐small cell lung cancer (NSCLC). Samples of 1,200 Chinese patients with NSCLC were analyzed through next‐generation sequencing to characterize the unique feature of uncommon EGFR mutations and ALK fusion. The results showed that 7.4% of EGFR‐mutant patients harbored both sensitizing and uncommon mutations and 11.6% harbored only uncommon mutations. Uncommon EGFR mutations more frequently combined with the genomic alterations of ALK, CDKN2A, NTRK3, TSC2, and KRAS. ALK fusion was more common in younger patients, and the frequency decreased monotonically with age. 3.2% of ALK‐positive patien...

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Section: Discussionsupporting

confidence: 87%

Genomic Signature of Driver Genes Identified by Target Next-Generation Sequencing in Chinese Non-Small Cell Lung Cancer

Dai

Wang

et al. 2019

The Oncologist

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“…The efficacy results are consistent with prior reports with EGFR inhibitors in this patient population, although relatively little information has been provided regarding the dose delivery, duration of therapy, and dose reductions from toxicity. Of concern, 3 patients in the study by Ni et al developed pulmonary toxicity, including a grade 5 event . Notably, in this phase 3 study of icotinib versus gefitinib, no cases of pulmonary toxicity were observed.…”

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confidence: 66%

“…Of concern, 3 patients in the study by Ni et al developed pulmonary toxicity, including a grade 5 event. 5 Notably, in this phase 3 study of icotinib versus gefitinib, no cases of pulmonary toxicity were observed. The higher predilection of Asian patients to develop pulmonary toxicity with EGFR tyrosine kinase inhibitors has been reported previously.…”

mentioning

confidence: 73%

“…The review by Liu et al provides an excellent summary of targeted agents currently under development for lung cancer in Chinese patients. 5 The authors noted that nearly 53% of patients with NSCLC in China do not harbor a driver mutation and currently are treated with chemotherapy. A number of novel agents that are specifically being developed in China, and are not familiar to the Western world, are described in their review.…”

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confidence: 99%

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Lung cancer in China: The new frontier?

Ramalingam

Khuri

2015

Cancer

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“…Significant efforts by the Chinese government during the last 2 years have led to improvements in the overall clinical research environment [14]. Now the CFDA is actively reforming the regulatory framework for the approval of novel agents, which has introduced a “four-color light” strategy and will likely further adjust its policies to reflect advances in large international clinical trials of immunotherapy [15].…”

Section: Domestic Clinical Trialsmentioning

confidence: 99%

Ongoing clinical trials of PD-1 and PD-L1 inhibitors for lung cancer in China

Liu

2017

J Hematol Oncol

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Compared to chemotherapy, promising results have been obtained by blocking the PD-1 pathway using antibodies that inhibit programmed cell death protein 1 (PD-1) or programmed cell death protein ligand 1 (PD-L1). Furthermore, global researchers and doctors are exploring how to optimize this immunotherapy in 270 clinical studies. However, Chinese clinical trials of these agents remain in the early stages. We summarize the ongoing international and domestic clinical trials using PD-1 and PD-L1 inhibitors to treat lung cancer. This information can help researchers better understand the active and approved clinical trials in China, as well as the ongoing research regarding PD-1 and PD-L1 inhibitors.

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Novel targeted agents for the treatment of lung cancer in China

Cited by 11 publications

References 53 publications

Genomic Signature of Driver Genes Identified by Target Next-Generation Sequencing in Chinese Non-Small Cell Lung Cancer

Genomic Signature of Driver Genes Identified by Target Next-Generation Sequencing in Chinese Non-Small Cell Lung Cancer

Lung cancer in China: The new frontier?

Ongoing clinical trials of PD-1 and PD-L1 inhibitors for lung cancer in China

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