Accurate management of EGFR-positive patients throughout the process

*It is only for medical professionals to read for reference.
How to make good use of "weapons" to make EGFR-positive patients live long? Among Chinese non-squamous non-small cell (NSCLC) lung cancer patients, 50% carry EGFR-positive mutations, among which exon 19 deletion mutations and exon 21 L858R point mutations are the main ones [1,2]
.

The latest guidelines [3] or expert consensus [4] unanimously recommend epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) as the first-line standard treatment for patients with advanced NSCLC with EGFR mutations
.

At present, a number of clinical studies have proven [5-8], compared with the traditional platinum-containing two-drug chemotherapy, the first-generation TKIs (gefitinib, erlotinib, icotinib), the second-generation TKIs (Afatinib, Dacomitinib) or third-generation TKIs (Osimertinib) have significant advantages in patients' PFS, OS, ORR quality of life, tolerability and other aspects
.

In the process of cancer treatment, first-line treatment plays an important role for the first time, but the importance of back-line treatment cannot be ignored
.

Therefore, how to choose the best sequential treatment mode in the whole course of treatment to bring patients the longest survival benefit and the best quality of life is the ultimate goal of the unremitting pursuit of clinicians
.

At present, patients with EGFR-mutant NSCLC have a wealth of first-line treatment options, and TKIs are in a state of "three generations on the same roof"
.

Previously, the first and second generations of EGFR-TKIs have been recommended by NCCN guidelines [9], ESMO guidelines [10], and CSCO guidelines [11]
.

The 2017 ESMO conference announced the PFS results of the third-generation TKIs osimertinib in the FLAURA study [12].
The study revealed that osimertinib has obvious PFS advantages over the first-generation TKIs (18.
9 vs.
10.
2) Month, HR=0.
46, 95%CI[0.
37-0.
57]; P<0.
001)
.

The OS results of FLAURA research results were announced at the 2019 ESMO conference [13].
Compared with the first generation of TKIs, osimertinib showed significant OS benefits (38.
6 months vs.
31.
8 months, HR=0.
80, 95%CI[0.
64-1.
00]; P=0.
046)
.

In addition, the overall safety of osimertinib is better than that of first-generation TKIs
.

Previously, after the first- and second-generation TKIs were resistant as first-line treatment, patients with T790M mutation-positive could receive third-generation TKIs osimertinib as a back-line treatment
.

With the success of Osimertinib and a generation of TKIs in the head-to-head PK (FLAURA study), Osimertinib was approved for the first-line treatment of EGFR-sensitive mutations, bringing hope to more lung cancer patients
.

About the authorProfessor Dong Xiaofang, Director of the Department of Oncology and Chief Physician, Dongyang People's Hospital, Member of the Pelvic Tumor Professional Committee of the Chinese Medical Education Association Member of the Zhejiang Academy of Mathematical Medicine Tumor Precision Diagnosis and Treatment Professional Committee Member of the Zhejiang Anti-Cancer Association Tumor Chemotherapy Professional Youth Committee Member of the Jinhua Anti-Cancer Association Oncology Nutrition Support and Treatment Professional Committee Vice Chairman Jinhua Anti-Cancer Association Medical Oncology Professional Committee Member, Jinhua Medical Association Oncology Branch Chemotherapy and Biotherapeutics Group Expert Comments "1+3", "2+3" and "3 +x" mode, who can go further? With the release of more and more research data, we can be sure that there are differences in the efficacy of EGFR TKIs in patients of different races and different gene mutation subtypes, whether it is the choice of medication for first-line treatment or post-line treatment.
Both require individualized considerations, and no model is universal
.

FLAURA's overall research results suggest that the "3+x" model is better than the "1+3" model in terms of effectiveness and safety
.

For the "2+3" treatment model, in the ARCHER1050 study comparing the second-generation TKIs with the first-generation TKIs head-to-head, the second-generation TKIs dacomitinib also showed PFS (14.
7 months vs.
9.
1 months, HR= 0.
59), 95%CI[0.
47-0.
74]; P<0.
001) and OS benefit 34.
1 months vs.
26.
8 months, HR=0.
76, 95%CI[0.
58-0.
99]; P=0.
044)[14]
.

It is worth noting that, unlike the FLAURA study, the ARCHER 1050 study did not include patients with brain metastases, and the side effects of dacomitinib were more obvious than that of the first generation, and the proportion of T790M in the posterior line was lower (about 10%).
The proportion of patients who can use osimertinib in the back line is even lower
.

Therefore, although the first-generation, second-generation and third-generation TKIs have guidelines to support their use in first-line treatment, the specific choice should be made by considering the effectiveness of the drug, the patient's tolerance to side effects, and drug resistance
.

It is certain that osimertinib plays an important role in realizing the long-term survival and improving the quality of life of NSCLC patients with EGFR mutations regardless of the treatment mode
.

Comment on the expert profile Professor Chen Lin, Chief Physician of the Department of Oncology, Sichuan Provincial People’s Hospital Graduated from the Department of Clinical Medicine of West China Medical University in 1993, and received a bachelor degree.
In June 2008, he received a master’s degree from the West China Medical Center of Sichuan University.
Member of the Anti-Cancer Association of the Chinese Medical Association.
Member of the Standing Committee of the Oral Head and Neck Tumor Special Committee of the Sichuan Provincial Administration of Traditional Chinese Medicine.
The leader of the cancer pain standardized demonstration ward presided over a provincial scientific research project and published many SCI papers.
May 2011 Participated in ESTRO-CSTRO Radio Physics and Clinical Joint treatment training, participated in cancer clinical work for 25 years
.

How can experts comment on TKIs after being resistant? Theoretically, after first- and second-generation TKIs are resistant, about 60% of patients develop T790M mutations, which meets the indications for sequential third-generation TKIs osimertinib, but only 14-16% of patients in the real world have the opportunity to use it.
Three generations of TKIs [14]
.

The main reason for this data gap is the unsatisfactory detection status of T790M mutation
.

In order to benefit more patients, it is necessary to make great efforts in the three aspects of testing timing, testing specimens and testing platform to increase the proportion of genetic testing of Chinese patients after drug resistance
.

Specifically, for the timing of detection, in the stage of disease progression, the progress of patients should be closely monitored, and genetic mutation testing should be performed in time for patients with rapid progress to avoid delaying the timing of treatment
.

For patients with slow progress and local progress, respectively continue TKI and continue TKI + local treatment [15] (CSCO guideline 2A evidence), after further development to rapid progress, the same as before, timely genetic testing
.

Secondly, with regard to test specimens, it is possible to improve the success rate of testing by improving tissue biopsy skills, using cytology or blood sample replacement, standardizing the sampling and inspection process, and strengthening testing quality control and other links
.

Finally, for the detection platform, try to choose a highly sensitive and fully validated platform, and it is recommended that patients with negative plasma be retested
.

For patients who are T790M negative and have no indications for sequential treatment of osimertinib, platinum-containing dual-agent chemotherapy is a category 1 recommended regimen in the CSCO guidelines [16]
.

For T790M-positive patients, early dressing change to receive osimertinib therapy can maximize the survival benefit
.

In addition, osimertinib has also been included in medical insurance, which not only achieves long-term survival and good safety, but also reduces the economic burden for patients
.

Comment on the expert profileProfessor Hu Xingsheng, Chief Physician, Professor, and Master Supervisor of the Department of Internal Medicine, Cancer Hospital of the Chinese Academy of Medical Sciences, Member of the Standing Committee of the Oncology Branch of the Chinese Medical Care International Exchange Promotion Association, Member of the Standing Committee of the Oncology Rehabilitation Professional Committee of the Chinese Association for the Development of Rehabilitation Technology Member of the Standing Committee of the Chinese Society of Geriatric Oncology Molecular Targeting Professional Committee Member of the Standing Committee of the Chinese Cancer Foundation Oncology Training Program Lecturer Group Lecturer of the Beijing Cancer Prevention and Treatment Research Society Translational Medicine Subcommittee Vice-Chairman "Journal of Clinical Drug Therapy" Editorial Board "China Medical Herald" Magazine Editorial Board Reference: [1].
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pdf Approval number CN-68498 Expiration date 2021-11-12* This article is only used to provide scientific information to medical professionals and does not represent the views of this platform