Prof. Zhou Caicun: ALK-TKI “competing for the best”, from the whole management of ALK-positive advanced NSCLC to see the first-line treatment drug selection


The number of patients with ALK-positive non-small cell lung cancer (NSCLC) accounted for ALK-positive advanced NSCLC, which accounts for 5% to 7% of the total lung cancer patients, is characterized by central nervous system involvement and brain metastases. Statistics show that the incidence of brain metastases in patients with ALK-positive advanced NSCLC is 23% to 31%1. In recent years, with the progress of driver gene research and molecular targeted personalized therapy, these patients have survived for more than three years or even longer, so the “chronic disease” of advanced lung cancer is gradually becoming a reality< span>2. At present, a variety of ALK tyrosine kinase inhibitors (TKIs) are in a situation of “three generations in the same family”. How to rationally arrange these drugs, play a big game of lung cancer treatment, and make patients live longer and better is the most concerned issue for clinicians and patients at present. In this regard, Yimaitong specially invited Professor Zhou Caicun from Shanghai Pulmonary Hospital to share about patients with ALK-positive advanced NSCLC full management experience, especially drug selection for first-line treatment.

Professional Profile

>Professor Zhou Caicun

  • Shanghai Pulmonary Hospital Affiliated to Tongji University

  • Executive member of the Chinese Society of Clinical Oncology

  • Chairman of the Thoracic Oncology Branch of the China Medical Promotion Association

  • International Lung Cancer Research Member of the Board of Directors of the Society (IASLC BOD)

  • Chairman of the Non-Small Cell Specialized Committee of the Chinese Society of Clinical Oncology

  • China Anti-Cancer Member of the Standing Committee of Lung Cancer Professional Committee of the Association

  • Vice Chairman of Shanghai Anti-Cancer Association

  • Lung Cancer Molecular Targeting of Shanghai Anti-Cancer Association and the chairman of the immunotherapy committee

  • the vice chairman of the cancer drug clinical research committee of the Chinese Anti-Cancer Association

  • China Member of the Standing Committee of the Oncology Branch of the Medical Association

  • Vice President of the Oncology Branch of the Shanghai Medical Association

  • Deputy Director of the Oncology Branch of the Shanghai Medical Association Member

  • Director, Institute of Oncology, Tongji University School of Medicine

  • Leading Talents in Shanghai

ALK’s full management is very important, and the second-generation ALK-TKI is still the front line Optimal

A variety of ALK-TKIs have come out one after another in the era of precision medicine. Survival was significantly prolonged. In the whole process of management of ALK patients, reasonable formation of troops becomes more and more important. Professor Zhou Caicun said that for the clinical drug selection of first-line treatment strategies for patients with ALK-positive advanced NSCLC, clinicians should consider drug efficacy, drug safety, and patient outcomes. Comprehensive consideration should be given to the characteristics of the disease (such as whether it is accompanied by brain metastases), the economics and social value of innovative drugs, etc. At present, the second-generation ALK-TKI is often used as a better first-line drug for the clinical treatment of patients with ALK-positive advanced NSCLC, especially brigatinib, which has more benefit from brain metastases Nitride, alectinib, etc., and other regimens should be followed after drug resistance.

Professor Zhou Caicun pointed out , PROFILE1014 study showed that the progression-free survival (PFS) of first-line treatment with crizotinib was only 10.9 months 3, and the survival period was shorter. In addition, patients with brain metastases at baseline have poor clinical outcomes, and the overall incidence of central nervous system (CNS) metastases after first-line crizotinib therapy can even reach 50%-60%4.

For patients with ALK-positive advanced NSCLC, the first-line efficacy of crizotinib is not satisfactory chronic disease” needs. To this end, ALK-TKIs with better clinical benefits and more benefits from brain metastases, such as brigatinib, alectinib, and lorlatinib, have emerged as the times require. So, is the third-generation ALK-TKI represented by lorlatinib preferred in clinical practice as a sequential regimen for first-line treatment?

Professor Zhou Caicun believes that the clinical data of lorlatinib is good, but it is immature and needs further observation. Combined with the current clinical experience, he suggested that lorlatinib should be used in the later line treatment, the important reason is that it has a relatively unique toxicity profile. In the CROWN study, 21% of patients had cognitive problems and 16% had mood-related adverse reactions5, which Psychiatric side effects often require concurrent treatment with a psychiatrist. At the same time, the research after lorlatinib resistance needs more exploration, and the sequential selection after compound mutation needs more data to support. As a result,Second-generation ALK-TKIs have become the mainstream first-line treatment options for patients with ALK-positive advanced NSCLC, especially brigatinib, Drugs such as alectinib are favored by clinical practice.

Brigatinib achieved significant benefits in patient survival and quality of life

Population-wide durable response

Professor Zhou Caicun pointed out that in the ALTA-1L study In the first-line population, median PFS (mPFS) exceeded 30 months, and brigatinib reduced the risk of disease progression or death by up to 57% (HR=0.43, P<0.0001)6 , excellent PFS data.

with tizoleBugnig Comparison of mPFS with tinib

strong benefit in brain metastases

Professor Zhou Caicun also introduced that, compared to gram Zotinib and brigatinib have better intracranial efficacy. Patients with brain metastases at baseline had a 75% lower risk of disease progression and death (HR=0.25, P < 0.0001)6< /span>, the 4-year overall survival (OS) rate of patients with brain metastases at baseline was as high as 71%7.

Good safety

Professor Zhou Caicun introduced that in addition to good efficacy data, Brigatinib has controllable safety and long-term tolerability. Grade 3/4 adverse events are mainly elevated laboratory blood test indexes, and most patients are asymptomatic 6.

Professor Caicun ZhouAdded that, it is worth noting that, in addition to the first-line benefit, sequential other treatment regimens after brigatinib resistance can still benefit continuously. A U.S. real-world study confirmed that multiple ALK-TKI regimens still provide patients with further survival benefits after brigatinib resistance. The time to quality of life deterioration (TTD) is 7.2 months, especially if lorlatinib is selected, the TTD can reach 8 months.8.

Sequential first-line treatment of second-generation ALK-TKI with better clinical benefit and more benefit from brain metastases such as brigatinib Modelprovides further survival benefit for patients with ALK-positive advanced NSCLC and optimizes the whole-course management of this patient population.


For patients with ALK-positive advanced NSCLC, under the background of whole-process management, how to maximize the benefits of first-line drugs has become the focus of clinical attention. Finally, Professor Zhou Caicun concluded that in the future clinical practice, there will be more choicesBugeta Second-generation ALK-TKIs with better clinical benefits and more benefits from brain metastases such as alectinib and alectinib are preferred as first-line treatments. To meet the urgent medical needs of the majority of patients with ALK-positive advanced NSCLC.


1. Li Caihe, Hu Changchen, Cheng Dongdong, et al. Brain metastases from non-small cell lung cancer. Advances in targeted therapy[J]. Evaluation and Analysis of Drug Use in Chinese Hospitals, 2022, 22(4):7.

2. [J]. Medicine and Philosophy (B), 2014,35(11):15-19.

3. olomon BJ, et al. N Engl J Med. 2014 Dec 4;371(23):2167-77.

4. Zou Z, Xing P, Hao X, et al. Intracranial efficacy of alectinib in ALK-positive NSCLC patients with CNS metastases-a multicenter retrospective study. BMC Med. 2022;20(1):12.

5. Camidge DR. Lorlatinib Should Not be Considered as the Preferred First- Line Option in Patients With Advanced ALK Rearranged NSCLC [J]. J Thorac Oncol, 2021, 16(4):528-531.

6. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib Versus Crizotinib in Advanced ALK Inhibitor-Naive ALK-Positive Non-Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial. J Clin Oncol. 2020;38(31):3592- 3603.

7. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib Versus Crizotin ib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L .

8. MO Jahanzeb, et al. 2021 ESMO 1205P.

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Approval code: C-APROM/CN/ALUN/0194

Approval date: July 2022

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