Ideological photos into reality!This real world study shows that Dakotinib has potential for EGFR no

*For medical professionals for reading reference

Dakatinib the treatment of EGFR non -sensitive mutations NSCLC real world research interpretation

In 2022, the Annual Meeting of the American Clinical Oncology Society (ASCO) was held in the form of online and offline conferences from June 3-7. As the largest and most authoritative academic conference in the tumor field, the ASCO Annual Conference has always been considered the "vane" of tumor treatment, attracting the attention of many scholars and experts at home and abroad.

Targeted therapy is currently the main treatment method of clinically targeting EGFR-positive non-small cell lung cancer (NSCLC), but the existing development and exploration of EGFR-TKI focusing on EGFR sensitive mutations, so Targeted therapy requires more attention. This year's ASCO Annual Meeting reported a real world research led by Professor Wang Yan, led by Professor Wang Yan, who was led by Professor Wang Yan of the Chinese Academy of Medical Sciences.

Take this opportunity, "Medical" invites Professor Wang Yan to discuss and analyze the clinical significance of this study and the current status of EGFR non -sensitive mutations NSCLC.

For EGFR non -sensitive mutations NSCLC,

Current clinical lack of high -level evidence

EGFR mutation is a relatively common genetic mutation type of NSCLC, and its incidence in Asian people is about 30%-50%[2]. The most common mutation type in EGFR positive NSCLC is 19 exogenous child lack mutations and 21 outer sub -L858R dot mutations. In addition, 12%-34%of EGFR positive NSCLC patients are typical or non-sensitive mutations [3-5], and the survival benefits of such patients after receiving targeted treatment are compared to EGFR sensitive mutations NSCLC patients are lower [6].

A post-analysis based on Lux-LUNG2, LUX-LUNG3 research, and Lux-lung6 research showed that Afutini was objective for EGFR18-21 outer-sensitive child-sensitive child-sensitive sub-sensitive mutations (L861Q, G719S, G719A, G719C, S768I) NSCLC. The relief rate (ORR) is 71.1%, the median without progress (PFS) is 10.7 months, and the median total survival period (OS) is 19.4 months [4]. In addition, there are phase II clinical studies that Oshitinib can be used to treat EGFR non -sensitive mutations NSCLC.

Professor Wang Yan pointed out that the main non -sensitive mutation types of EGFR include EGFR G719X, S768i, L861Q mutations, etc. Due to the low incidence of non -sensitive mutations in EGFR and many types, most clinical research has not been included in such patients. In addition, although some data prompts, EGFR-TKI may benefit patients' survival, but the existing clinical research on EGFR non-sensitive mutations NSCLC is mostly studied by small samples [8-10]. Therefore, the National Comprehensive Cancer Network (NCCN) NSCLC Clinical Practice Guide [11] Although multiple targeting drugs are recommended to treat the NSCLC people with EGFR S768i, L861Q, G719X mutations, due to the lack of high -level research evidence, the recommended level is recommended Not high.

It is worth noting that there are currently some data prompts that EGFR-TKI single drugs or combined chemotherapy may bring better efficacy to patients with non-sensitive mutations in EGFR. As a second-generation EGFR-TKI, it has shown certain potential among some patients with non-sensitive mutations in EGFR, and how this potential is worthy of in-depth investigation. This is the original intention and purpose of our team to conduct this study. Professor Wang Yan Add. The sword refers to the non -sensitive mutation of EGFR, and the effect of Dakininib showed the initial showing

This time, a study reported by Professor Wang Yan's team in the ASCO Annual Conference included 38 NSCLC patients carrying EGFR non -sensitive mutations. Thirty patients carry non -sensitive mutations in the main EGFR non -sensitive mutations in the clinically "common", including G719A/C mutations (13 cases), S768i+G719A/C/s mutations (8 cases), L861Q mutations (7 cases), and L861Q+G719A mutation (2 cases), and 8 other patients carry more rare non -major EGFR non -sensitive mutations, namely E709X mutations (3 cases), L747P mutations (3 cases), H183D mutations (1 case), and and and. G598V mutation (1 case).

The results of the study showed that after treatment, patients with 55.3%(21/38) were relieved, and patients with 89.5%(34/38) were controlled. The patient's median PFS reached 10.3 months (95%CI 5.8–14.8 To. For patients carrying non -sensitive mutations, 62.5%(5/8) and 87.5%(7/8) patients were relieved or controlled. In addition, it is worth noting that among patients with brain metastases, 88.9%(16/18) patients with intracranial metastases are controlled, and the median PFS is 6.6 months (95%CI, 6.3–6.9).

Regarding this study, Professor Wang Yan said that the following points were impressed by his feelings:

1. In the "pre -trial" before the formal research, it can be observed that some NSCLC patients carrying EGFR non -sensitive mutations clinically in the clinic, after other treatments cannot obtain satisfactory effect, choose to try to receive Darkitinib therapy, even if even Putting on back -line therapy, Dakotinib can also show a good effect [12], so for patients with significant benefits to receiving first -line targeted therapy, you can consider using Dakotinib for treatment as soon as possible after drug resistance. [ 13]. At the same time, there are related in vitro experiments that Dakotinib may have a certain potential for patients with drug resistance due to secondary L718X and L792X mutations after receiving Oshitinib. This study adds more confidence.

2. Among patients with NSCLC who carry EGFR non -sensitive mutations, there are many patients with composite mutations with multiple mutations at the same time. Whether this will affect the effect of the patient's acceptance of Dhakitinib is one of the focus of the institute's attention. Fortunately, according to the existing research data, the efficacy of Dakatinib has not been significantly affected for patients with compound mutations. Not only that, another real world study of our team also reminded that Dakotinib can produce good effects and safety on multiple EGFR mutant subtype patients [13].

3.Rcher 1050 Study [15,16] confirmed the efficacy of Darkitinib for EGFR 21 exogenous L858R mutations NSCLC, but the study was not included in patients with brain metastases. Controlling patients in the furnace is a matter of widespread attention. At present, some studies have proved that Darkitinib has certain effects on patients with brain metastases [17]. Related research conducted by our team also indicates that Darkitinib has good activity and tolerance for patients' intracranial lesions [[ 13], and the real world research reported by our team at the ASCO conference further confirmed that Dakotininib did have good brain activity.

Dance research may make up for forward -looking research

Inadequate data

Professor Wang Yan believes that although this real world study reminds Darkitinib to have certain clinical application prospects for EGFR non -sensitive mutations NSCLC, providing relevant clinical experience and evidence for clinical workers in tumor, but its level of evidence is limited. In the future, the clinical practice and rewriting guide will still need to be further conducted.

In addition, for those patients with different EGFR-TKIs for mutations, non-sensitive mutant patients have a mechanism for drug resistance, how to formulate the next treatment plan after drug resistance, and how to manage such patients throughout the process. Both need to be further explored and "benchmark" with EGFR sensitive mutations related treatment models.

The current Dance Study [18] is a forward -looking phase II clinical study designed to evaluate the treatment of EGFR non -sensitive mutations in the advanced period of NSCLC. After 6 weeks of treatment, the tumor relief depth was close to 50%during the first curative effect evaluation, and there was no obvious adverse reaction. In this regard, Professor Wang Yan also said that he hopes that Dance research in the future can supplement the previewing research data and provide more basis for clinical treatment of EGFR non -sensitive mutations NSCLC. Summarize

At present, whether EGFR-TKI can bring survival benefits for EGFR non-sensitive mutations NSCLC patients, it still lacks high-level evidence support. The real world research reported by Professor Wang Yan's team at the ASCO Annual Meeting shows that Darkitinib has a good clinical application prospect for EGFR non -sensitive mutations NSCLC, but in the future, further forward -looking research is needed to change clinical practice.

Expert Introduction

Professor Wang Yan

Internal Medicine of Cancer Hospital of Chinese Academy of Medical Sciences

Chief physician, doctoral tutor

Director of the China Clinical Oncology Society (CSCO)

Member of the Professional Committee of the China Anti -Cancer Association

Chairman of the Beijing Cancer Prevention Research Association Transformation Medical Association

Deputy Chairman of the Professional Committee of the Beijing Anti -Cancer Association

Deputy Chairman of the Beijing Cancer Prevention Society of Cancer Cancer Immunotherapy

Deputy Chairman of the Professional Committee of the Beijing Oncology Society

Standing Committee Member of the Beijing Cancer Prevention Research Association Drug Adverse Reaction Management Sub -Committee

Editor -in -chief of "Chinese Cancer Magazine" and "Chinese Version of the British Medical Magazine"

references

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*This article is only used to provide scientific information to medical people, and does not represent the viewpoint of this platform

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