2022 WCLC 丨 ≥2 Skin AE can be used as a prognostic logo?Update interpretation of Dakatinib research progress

*For medical professionals for reading reference

What did 2022 WCLC say about Dakatinib?

The occurrence of targeted therapy has brought disruptive changes to the treatment structure of advanced non-small cell lung cancer (NSCLC), and the widespread application of epidermal growth factor receptor (EGFR) -atheosine kinase inhibitor (TKI), which is positive for EGFR positive The survival benefits of NSCLC patients have brought great improvements. The lack of Xianzi (19DEL) and No. 21 outer L858R (21 L858R) mutation is the more common type of EGFR mutation in the clinic. It has unique advantages.

This year, some scholars in WCLC reported the analysis of the Archer 1050 after the analysis [1]. Take this opportunity. "Medical" specially invited Professor Yang Zhe, Shandong Provincial Hospital, to conduct the clinical effects, advantages and domestic applications of Dakotinib Analysis and interpretation.

Dakatinib became the ideal choice for 21 L858R mutations

In 2009, IPASS Studies [2] found that the efficacy of EGFR positive NSCLC was better than chemotherapy, and it opened the prelude to lung cancer targeted therapy. In the EGFR mutation type, 19DEL and 21 L858R are the most common, accounting for about 90%of EGFR mutations [3]. However, multiple studies have shown that the efficacy of different EGFR-TKI treatment of 19DEL and 21 L858R mutations has different effects. Generally speaking, the benefits of the non-progressive survival (PFS) and overall survival (OS) of 19DEL patients are better than 21 Patients with L858R mutations [4].

ARCHER1050 Studies are a period of III in the International Multi -Center. Clinical studies of open labels are designed to evaluate the efficacy and safety of Dakitinib or Gefitinib first -line therapy for EGFR mutations positive NSCLC patients [5]. ARCher 1050 studies show that compared with Geffitinib, Dakotinib can effectively extend the median OS (34.1 month vs. 27.0 months, HR 0.748, 95% CI: 0.591-0.947, bilateral P = 0.0155 ), OS benefits for 21 L858R mutations are also obvious (32.5 months vs. 23.2 months, HR 0.665, 95% CI: 0.470-0.941, bilateral P = 0.0203).

In this regard, Professor Yang Zhe said that Dakatinib is currently one of the few EGFR-TKIs that can benefit significantly OS, and similar results can also be observed in patients with 21 L858R mutations. At present, domestic and foreign guidelines such as "China Clinical Oncology Society (CSCO) Non -small Cell Cancer Diagnosis and Treatment 2022" and "National Comprehensive Cancer Network (NCCN) Non -small Cell Cancer Clinical Practice (2022.V3)" will be replaced by domestic and foreign guidelines. Nile is a first -line treatment for the first -line treatment of patients with EGFR sensitive mutations in NSCLC.

At the same time, "Consensus on the Starting Treatment of Local Advanced Local Advanced/Transferred Non -small Cell Cancer" [5] pointed out that in the process of clinical practice, different treatment plans should be given according to the type of patient mutation and brain metastases. Karkatinib and other schemes are given priority. Based on the above -mentioned guidelines, it can be further explained that Dakatinib is an EGFR sensitive mutation, especially the ideal choice of 21 L858R mutations, and it is also an ideal choice for Chinese patients.

Can skin -related AE be a prognostic symbol for patients? 2022 WCLC what did you say?

Many people think that "the medicine is three -point poison", so the adverse reactions (AE) produced during the treatment often become a "stumbling block" for tumor patients to achieve good results. EGFR has many effects on skin physiology, including stimulating the growth of the epidermis, suppressing differentiation, and accelerating wound healing. The activity of EGFR can lead to a level connection reaction of the intracellular signal transition pathway, so most EGFR-TKI, including Dakotinib, may cause a variety of adverse skin reactions [6].

But for anti -tumor treatment, does all AE mean bad prognosis? Not that. A foreign research reported [7] found that among patients with metastatic renal cell carcinoma treated by Schunitinib, hypertension caused by Schunitinib was related to patients' better clinical prognosis. In addition, a similar prompt can be obtained by an ARCHER 1050 research reported by WCLC this year [1].

The analysis results show that patients with ≥2 skin -related AE have occurred during the treatment, of which OS and PFS are better than patients with AE -related AE -related AE (PFS: 16.0 months vs. 9.2 months, HR 0.639, 95% CI: 0.439-0.928, P = 0.0086; OS: 37.7 months vs. 21.6 months, HR 0.548, 95%CI: 0.381-0.789, P = 0.0086).

Not only that, patients with AE -related AE -related AE appear, and their objective relief rate (ORR) is also better than patients without AE -related AE -related AE. In patients with ≥2 skin -related AE (n = 162), 11 patients were fully relieved (CR), 119 patients were partially relieved (PR), and ORR reached 80.2%. In the patients of AE (n = 65), only one patient obtained CR, 39 patients obtained PR, and ORR was 61.5%. Professor Yang Zhe pointed out that this study shows that patients receiving Dharobitinib therapy will be ≥2 skin -related AE or may obtain better efficacy during the treatment process. The prognostic symbols for the treatment of Dakotinib are used to predict the treatment of patients. Understanding the relationship between AE and clinical efficacy can help doctors correctly understand the drug AE in the clinic, bring better survival benefits to patients, and can also reduce the fear of patients for AE and enhance confidence in medication.

EGFR positive NSCLC clinical diagnosis and treatment will be more accurate

Professor Yang Zhe pointed out that Dakatinib, as the second-generation EGFR-TKI, can bring significant survival benefits to patients compared to Geffitinib [5]. This year's research progress reported by WCLC on Dakotinib once again proved the effectiveness of Darkitinib to treat EGFR positive NSCLC, and related research progress also brought some thoughts to clinical clinical.

The results of the after -after analysis of the Archer 1050 research preliminary reminding us that ≥2 -level skin -related AE may become a prognostic symbol for patients receiving Da Kotinib therapy. Except for ≥2 skin -related AE, whether there are others that can be used to predict patients' prognosis prognosis The logo needs to be discovered further. In addition, the analysis also indicates that each tumor clinical worker needs to dialectically treat the drug -related AE, thereby fighting for better results for patients.

Today, EGFR-TKI has been "three generations of the same hall". Patients have become increasingly rich after drug resistance. How to queue up for the best management is the focus of clinical diagnosis and treatment at this stage. Different drug -resistant mechanisms also determine different sequential treatment solutions. The value of 1+2+3, 2+3, 3+x and other solutions in different groups is still worth our further exploration.

Expert Introduction

Chief physician of Yang Zhe

Shandong Provincial Hospital

Chief physician, doctor of medicine, doctoral supervisor

Deputy Director

Chairman of the Shandong Provincial Society of Old Medical Society on Cancer Multi -Disciplinary Disciplinary Discharge and Treatment

Deputy Chairman of the Shandong Medical Association Precision Medicine Branch

Deputy Chairman of the Shandong Medical Association Cancer Precision Medical Medicine Branch

Deputy Chairman of the Radiation Oncology Branch of the Shandong Provincial Anti -Cancer Association

Member of the Lung Cancer Group of the Cancer Radiotherapy Committee of the China Anti -Cancer Association

Deputy Chairman of the Biostatic Treatment Committee of Shandong Province

Director of the Council of the Shandong Provincial Clinical Oncology Society

Approval number: PP-DAC-CHN-0866 Expired Day: 2023-8-10

references:

[1] Juan Li, Xingxiang Pu, Bo ZHANG, ET Al. Post HOC Analyses of Dacomitinib-Associated Skin Disorders and Effical in the Archer 1050 STUDY, ABSTRACT EP08.02-159-159.

[2] MOK TS, Wu yl, Thongprasert S, et al. Gefitinib or Carboplatin-Paclitaxel in Pulmonary Adenocarcinoma [J]. N Engl J Med. 2009, 361 (10): 947-57.

[3] Murray S, Dahabreh IJ, Linardou H, et al. Somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor and tyrosine kinase inhibitor response to TKIs in non-small cell lung cancer: an analytical database[J]. J Thorac oncol. 2008, 3 (8): 832-9.

[4] Wu Yilong, Lu Shun, Cheng Ying, et al. Unsplexed local advanced/metastatic non-small cell lung cancer starting therapy consensus [J]. Evidence-based medicine, 2020, 20 (03): 129-134.

. Drugs. 2021, 81 (2): 257-266. [6] Hu Jie, Lin Lizhu, Luo Xiaoqun, waiting for the consensus of adverse reaction management experts in .egfr-TKI [J]. China Lung Cancer Magazine, 2019, 22 (02): 57-81.

[7] Rini Bi, Cohen DP, Lu Dr, Et Al. Hypertension as a biomarker of eFFICacy in Patients with metastatic renal carcinoma time sunib [J].Then, then, then

*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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