How to choose EGFR-TKI targeted therapy?

*For medical professionals to read and refer to Chinese scholars to draw EGFR-TKI toxicity profile to help individual treatment choices.

Recently, the First Affiliated Hospital of Guangzhou Medical University, Professor He Jianxing and Professor Liang Wenhua of the National Respiratory Medicine Center are the co-corresponding authors and published the title Toxicity profile of epidermal growth factor receptor tyrosine in Critical Reviews in Oncology/Hematology (IF=5.
83).
kinase inhibitors for patients with lung cancer: A systematic review and network meta-analysis article, systematically summarized the toxicity of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) targeted therapy for lung cancer, from each Based on the systemic adverse events and specific adverse events of EGFR-TKI, a toxicity profile used to guide clinical practice was drawn.

 Screenshot of the title of the article More than ten years, the targeted drug EGFR-TKI has brought revolutionary changes to the treatment of lung cancer.
At present, it has included a generation of Gefitinib, Erlotinib and Erlotinib.
Icotinib, the second-generation Afatinib and Dacomitinib, and the third-generation Osimertinib are used clinically.

 A clear understanding of the toxicity of EGFR-TKI is essential to maximize its efficacy.
Especially in the current development, EGFR-TKI is not only the standard treatment for patients with EGFR mutation-positive advanced lung cancer, but also an adjuvant treatment for early patients after surgery.
With new choices, and the increase in drug exposure time, the probability of long-term accumulation of toxicity will increase.At the same time, as various new drugs continue to enter the clinic, the treatment background of patients has become more complicated.
For example, the use of immunotherapy involves the amplification of EGFR-TKI toxicity.

The study collected the data of 13,352 lung cancer patients from 40 phase II and III randomized controlled trials, and used the method of network meta-analysis to construct the pairwise comparisons between the above-mentioned multiple EGFR-TKIs, so as to obtain the comparison of each EGFR-TKI Whether the toxicity of other EGFR-TKIs is stronger or weaker is the result.

 The main assessment endpoints of the network structure chart include systemic adverse events (adverse events of any grade, adverse events of grade 3 or above) and specific adverse events (a total of 18 types: rash, vomiting, anorexia, etc.
).
Different EFGRs can be explained through direct or indirect comparison -TKIs have differences in the risk of toxicity, differences in severity, and their unique tendencies.

The results showed that icotinib produced the least any adverse events of any grade (followed by gefitinib) and adverse events of grade three or above (followed by osimertinib); each EGFR-TKI has its tendency to toxicity Sex (compared to other EGFR-TKIs).

Toxicity characteristics of different EGFR-TKIs Note: The specific toxicity of a certain EGFR-TKI cannot be included in the comparison between drugs, such as the cardiotoxicity EGFR-TKI meta-toxicity profile favored by osimertinib.
This study is currently aimed at EGFR -TKI is the safest and most comprehensive assessment of targeted treatment of lung cancer.
Through horizontal comparison between studies, accurate toxicity levels are calculated, providing a powerful safety reference for individualized targeted therapy of lung cancer.
Guide clinical practice well.

Researcher's view Professor Liang Wenhua: In 2019, our team published a network meta-analysis in BMJ to compare the first-line efficacy of different EGFR-TKIs and treatment combinations.

However, the precise selection of EGFR-TKI requires comprehensive consideration in combination with the toxicity of TKI in different usage scenarios, in addition to the curative effect.

Therefore, we further refined the analysis for toxicity and obtained the toxicity characteristics of different TKIs.

Based on this, individualized choices can be made for specific application scenarios that appear in some new situations: 1.
For patients with underlying diseases, drugs that have less impact on the corresponding organs should be selected, such as liver insufficiency or liver disease.
Patients with underlying diseases should avoid TKI with strong hepatotoxicity.

Especially in recent years, combined therapy (chemotherapy, anti-vascular, etc.
) has become more common, and the toxicity may be superimposed and amplified, and more caution is needed.

2.
It is used in postoperative adjuvant therapy, usually for more than 2 years, and some toxic and side effects with cumulative damage, such as liver toxicity and bone marrow toxicity, should be avoided as much as possible.

3.
Even for patients with EGFR mutations, immunotherapy such as PD-1 monoclonal antibody is still inevitable.
There are also problems of trying after drug resistance, or TKI challenge after PD-1 monoclonal antibody, and even EGFR-TKI that has not been completely abandoned.
Combined with the exploration of PD-1 monoclonal antibodies, it is urgent to guard against the fatal toxicity (lung, liver, etc.
) that may be amplified in the immune activation state, so as to make a relatively safe choice.

 The correct use of this "toxicity map" can facilitate physicians to communicate and explain with patients before EGFR-TKI medication, and remind physicians to pay more attention to the patient's basic physical conditions; during EGFR-TKI medication, they can be more directional Monitoring the toxicity of EGFR-TKI (such as paying more attention to more inclined toxicity) is conducive to early recognition and early treatment, which is particularly important for certain fatal toxicity (such as interstitial pneumonia); When toxicity occurs, especially when targeted intervention is ineffective and another EGFR-TKI needs to be changed, the alternative drug with the lowest toxicity tendency is selected.

In addition, the newly-listed Ametinib, Fometinib and other data need to be updated and included.

 Principal investigator He Jianxing, Dean of Guangzhou Institute of Respiratory Health, Director of National Respiratory Medicine Center, Deputy Director of National Research Center for Respiratory Diseases, Director of Thoracic Surgery, First Affiliated Hospital of Guangzhou Medical University, Academic Leader of Lung Cancer Group, State Key Laboratory, State Council Special allowance expert, central health committee, young and middle-aged experts with outstanding contributions from the Ministry of Health, Nanyue Baijie, China's top ten word-of-mouth physicians, American and British College of Surgery Fellow (FACS, FRCS), the first chairman of the Thoracic Surgery Branch of the Guangdong Medical Association, Executive editor of J Thorac Dis, editor in chief of Ann Tranl Med.

One of the founders and guideline makers of minimally invasive thoracic surgery in China, achieved full coverage of thoracoscopic thoracic tumor surgery in 2009; carried out minimally invasive thoracic surgery under spontaneous breathing anesthesia in 2011; it was the first in China to propose a combination Realized tubeless thoracic surgery, and revolutionized part of thoracic surgery into day surgery.

Focusing on clinical, basic and translational research related to lung cancer surgery, with more than 10,000 cases of chest surgery including combined cardiopulmonary transplantation, lung transplantation, minimally invasive lung cancer surgery, etc.
, in NEJM, Lancet, BMJ, Nat Med, JCO and other top international journals Published 334 SCI papers with a total impact factor of 1500+, and has been cited more than 15,000 times; edited 8 English monographs and 4 Chinese; obtained 10 invention patents and 50 utility model patents, including 3 international invention patents; There are 1 second prize of National Science and Technology Progress Award, 3 national innovation prizes, and 3 first prizes of provincial and ministerial science and technology awards.

Liang Wenhua, Deputy Chief Physician, Associate Professor, Ph.
D.
Supervisor/Postdoctoral Coordinator, National Natural Science Outstanding Youth Fund winner, Young Pearl River Scholar, Guangdong Outstanding Young Medical Talent Graduated from Sun Yat-sen University Cancer Prevention and Treatment Center, and now works in the First Affiliated Hospital of Guangzhou Medical University.

Mainly engaged in comprehensive diagnosis and treatment of lung cancer and translational research.
From 2012 to 2020, he published more than 150 international authoritative papers such as BMJ, J Clin Oncol, Lancet Oncol, NEJM, JAMA Intern Med, J Thorac Oncol, and 9 papers with a score of 20 or more.
The impact factor is over 750 points, the total number of citations is 3000+, and the H index is 27. Secretary-General of the Guangdong Society of Thoracic Diseases and Chairman of the Committee of Immunotherapy, Deputy Chairman of the Precision Therapy Branch of the Guangdong Medical Association, and Deputy Leader of the Lung Cancer Group of the State Key Laboratory of Respiratory Diseases.

CSCO Youth Member, Member of Lung Cancer Special Committee, Artificial Intelligence Special Committee, Member of CSCO Lung Cancer Guidelines Expert Group.

Winner of the ASCO Merit Award, the most promising young oncologist at CSCO “35 under 35” in 2018, Deputy Editor-in-Chief of Transl Lung Cancer Res (IF 5.
1).

As one of the accomplishers, he won the second prize of the National Science and Technology Progress Award, the National Innovation Award Medal, the 2020 Ali Green Orange Award, and the "National Famous Doctor" young talent.

Zhao Yi, Guangzhou Medical University, 2020 Ph.
D candidate, Harvard Medical School Graduate Medical Education HICR Semi-annual Exchange Program (2020-2021) AME Magazine Office SCI Paper Manuscript Reviewer Guangdong Province Outstanding Student, National Scholarship (Graduate Stage), Co-published first author SCI 6 papers (with a total impact factor of 57.
568), including BMJ, Clin Microbiol Infec, Ann Thorac Surg and other top international comprehensive or professional journals.
Research on the best treatment model for stage IIIA-N2 lung cancer was included in the international authoritative peer-reviewed website F1000 Recommendation; a total of 4 papers by the author (a total of 40.
214 impact factors).