Professor Zhang Li: J-ALEX is researching and reforming the idea of ​​ALK inhibitors "arranging troops", "drugs" can achieve the greatest benefit by making the best use of them. 2021 ASCO

*Only for medical professionals to read and refer to the final OS data of the J-ALEX study.
The five-year survival rate of the crizotinib group is as high as 64.
11%! ALK fusion is an important therapeutic target for advanced non-small cell lung cancer (NSCLC), and is known as the "diamond mutation"
.

With the advent of ALK inhibitors, the prognosis of ALK-positive NSCLC patients has been significantly improved, and the median overall survival (OS) has gradually increased
.

In 2011, the first ALK-TKI crizotinib was approved.
The PROFILE1014 study confirmed that the efficacy of first-line crizotinib was better than platinum-containing dual-agent chemotherapy, and the median progression-free survival (PFS) was significantly prolonged (10.
9 months vs 7.
0) Months, P<0.
001) [1]
.

Since then, the second-generation ALK-TKI aletinib and ceritinib have been approved for first-line treatment indications in China
.

With the increase in medication options, how to deploy first-generation and second-generation ALK-TKI in the real world to maximize the survival benefits of patients has also attracted clinical controversy and concern
.

 At the 2021 American Society of Clinical Oncology (ASCO) annual meeting, the Japanese J-ALEX study announced 68-month (5.
6 years) follow-up data.
The results showed that the five-year survival rates of crizotinib and aletinib were 64.
11% vs 60.
85, respectively.
%[2]
.

The "medical community" sincerely invites Professor Zhang Li from Peking Union Medical College Hospital to deeply interpret the results of the J-ALEX study and its implications for clinical practice in China
.

 The wonderful video of Professor Zhang Li looks at the essence of the J-ALEX study.
Professor Zhang Li said: "The five-year follow-up data of the J-ALEX study announced at this ASCO conference shows that the five-year survival rate of the crizotinib group and the aletinib group is extremely equal.
, Even the absolute data of the crizotinib group has increased to a certain extent
.
It
can be said that it has given a very big impact to the past model formed in clinical practice in China
.

At the same time, it has also triggered our thinking about clinical work.
Why did such a result occur? It is very necessary to review the design of the J-ALEX study and comparison with previous similar clinical studies
.

"The J-ALEX study included age ≥20 years old, without any ALK-TKI treatment, stage IIIB/stage V/relapsed ALK+ NSCLC patients, and allow enrolled patients to receive a previous chemotherapy regimen
.

"From the perspective of administration measures, since the J-ALEX study is aimed at Asian populations with small body weight or small body surface area, the dose of aletinib is adjusted to 300 mg bid, while crizotinib is still the classic and conventional 250 mg bid.
Dosage, such adjustment can be said to be more humane and individualized
.

" Professor Zhang Li said
.

Judging from the baseline characteristics of the enrollment of the two groups, the ratio of 27.
9% of patients with brain metastases in the crizotinib group was significantly higher than the 13.
6% in the aletinib group, which is also somewhat different from previous similar studies
.

But the most worth mentioning is that the J-ALEX study design allows crossover between the two groups, which means that when the disease of the patients initially assigned to the crizotinib group progresses, aletinib can be crossed over
.

Professor Zhang Li said: "Such a research design is more in line with the prescriptions and procedures of patient diagnosis and treatment in the real world," and it can also provide certain guidance on the timing of ALK-TKI medication
.

Figure 1 The design of the J-ALEX study and the characteristics of the enrolled patients "old trees sprout", more potential benefits to be discovered.
The final overall survival (OS) data reported at the ASCO conference shows: the median of the aletinib group The follow-up time was 68.
8 months, the median follow-up time of the crizotinib group was 68.
0 months, and the number of deaths was 40.
8% (alatinib group) and 39.
4% (crizotinib group), so the two groups There is no value for OS, only 5-year survival rate, 60.
85% (alatinib) vs 64.
11% (crizotinib), HR 1.
03 (95% CI, 0.
67-1.
58) (Figure 2)
.

Figure 2 The final OS results of the J-ALEX study Professor Zhang Li said: "The five-year survival data of the two groups are surprisingly similar.
The five-year survival rate of the J-ALEX study crizotinib group is also extremely large compared to the data of the ALEX study.
increase
.

so in future clinical application of them, should be reasonable application generation ALK-TKI erlotinib azole grams, were reasonably formations and second-generation TKI, such as J-ALEX study in first-line use of azole grams imatinib, second-line use a Letinib ultimately achieves patient survival benefits
.

We also hope that after further optimization of the application model of ALK-TKI, the therapeutic potential of crizotinib can be tapped to achieve the effect of'old trees sprouting new buds'
.

" J -The ALEX study "polished" the Chinese clinical treatment thinking.
The design of the J-ALEX study and the ALEX study are similar, but the 5-year survival rates of the two studies are somewhat different.
They are 60.
85% of aletinib vs.
crizotinib, respectively.
64.
11% (J-ALEX); Aletinib 62.
5% vs Crizotinib 45.
5% (ALEX)
.

The reason behind this difference, Professor Zhang Li said: "First, the sequential rate is different.
Crossover is not allowed in the design of the ALEX study.
Therefore, the proportion of second-line drugs that can be used in the ALEX study is lower than that in the J-ALEX study
.

In the J-ALEX study, 82.
7% of the patients in the crizotinib group received sequential ALK-TKI treatment, and 78.
8% of the patients received cross-over treatment with aletinib
.

(Figure 3)” Figure 3 Sequential use of drugs in the J-ALEX study As the experimental design does not allow crossover in the ALEX study, the sequential use of aletinib in the crizotinib group had certain difficulties under the circumstances: Accessibility is limited; the economic burden affects patients' second-line medications.
These reasons have led to a low proportion of other AKI-TKIs in the crizotinib group in the crizotinib group in the ALEX study
.

 With the update of medical insurance policies, the second-generation TKIs are adapted to The first-generation ALK-TKI crizotinib sequential second-generation TKI in the J-ALEX study is closer to the real-world medication situation, and the research results also show that this sequential model can also be used for patients.
" "Stroke" will have a long-term overall survival benefit
.

"This model is more in line with the current "full-course" treatment concept, first-line and second-line sequential use, so that each drug can do its best
.

"Professor Zhang Li added
.

 Professor Zhang Li said: "The J-ALEX study shows that crizotinib, as a first-line treatment, can also enable patients to achieve long-term survival while ensuring a reasonable ALK-TKI formation
.

Even for these patients with brain metastases, the first-generation TKI and the second-generation TKI were replaced in time under close monitoring, and their survival was not significantly affected
.

The release of the data of the J-ALEX study has a huge "cleansing" effect on the clinicians' previous cognition, allowing them to have a clearer and thorough understanding of the formation of the first and second generation ALK-TKI
.

"Expert profile Professor Zhang Li, chief physician of the Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, doctoral tutor, and well-known professor.
In 2015, as the fifth complete person, he won the "National Science and Technology Progress First Prize".
In 2017, he won the Respiratory Disease Branch of the Chinese Medical Association.
"Outstanding Respiratory Academic Contribution Award" won the China Association for the Promotion of Pharmaceuticals.
In 2019, "Dushu Lake Cup" Pharmaceutical Innovation "Most Influential Drug Clinical Research Leader Award" 2020.
1.
22 won the first prize of Tianjin Science and Technology Progress Award 2020.
7.
25 Won the second prize of the Science and Technology Award of the Chinese Anti-Cancer Association.
Won the Hospital Medical Achievement Award for many times.
Interdisciplinary Sciences: Computational Life Sciences Associate Editor (SCI 1.
46) Member of the Lung Cancer Group of the Chinese Medical Association Member of the Chinese Lung Cancer Alliance Member of the Beijing Branch Vice Chairman of the China Lung Cancer Prevention Alliance Chairman of the Immunotherapy Committee Beijing Medical Award Foundation Brain Metastasis Special Committee Deputy Chairman CACA Tumor Microenvironment Specialty Committee Standing Committee CSCO Tumor Cardiology Specialist Committee Standing Committee Member of the Chinese Thoracic Tumor Research Collaboration Group (GACT/CTONG) Member of China Medicine Member of the Standing Committee of the Anti-tumor Drug Clinical Research Committee of the Innovation Promotion Association Member of the Chinese Respiratory Tumor Collaboration Group Member of the Chinese Society of Interdisciplinary Science Member of the Sixth Editorial Committee of China Respiratory Journal Member of the Editorial Committee of China Lung Cancer Journal Member of the Sixth Editorial Committee of International Respiratory Journal Chinese Medicine "Chinese Journal of Clinicians (Electronic Edition)" Expert Committee Standing Committee Member of the Internet of Things Medical Professional Committee of China Non-Public Medical Institutions Association Standing Committee Member of the Lung Cancer Subcommittee of the Geriatric Oncology Committee of the Chinese Society of Gerontology Beijing Cancer Research Association/Lyyin Salon Cancer Research Reference materials for members of the collaboration group: [1]] WU YL, LU S, LU Y, et al.
Results of PROFILE 1029, a Phase III Comparison of First-Line Crizotinib versusChemotherapy in East Asian Patients with ALK-Positive Advanced Non-Small CellLung Cancer .
J Thorac Oncol,2018, 13(10): 1539-1548.
[2]https://meetings.
asco.
org/abstracts-presentations/198351*This article is only used to provide scientific information to medical professionals and does not represent the views of this platform