Professor Wang Zhijie: The sword is sheathed, ALK-TKI is in full swing, and bugotinib stands out, opening up a new pattern of treatment for patients with ALK-positive NSCLC brain metastases

preface

With the advent of the era of targeted therapy, anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKI) continue to develop, and the diagnosis and treatment of ALK-positive non-small cell lung cancer (NSCLC) has entered a "chronic" development

Based on the stunning data from the ALTA-1L study, it was officially approved by the State Food and Drug Administration on March 22, 2022 for the treatment

Expert Profiles

Professor Wang Zhijie

• Chief Physician of the Department of Internal Medicine, Cancer Hospital, Chinese Academy of Medical Sciences

• Selected as a young top-notch talent of the national "Ten Thousand People Plan" and a rising star of science and technology in Beijing

• Author of the CSCO Guidelines for the Diagnosis and Treatment of Non-Small Cell Lung Cancer

• Member of the National Antineoplastic Drug Clinical Application Monitoring Committee

• Member of the Lung Cancer Quality Control Expert Committee of the National Cancer Quality Control Center

• Director of the Chinese Society of Clinical Oncology (CSCO).

  
  

• Member of the Standing Committee of the Non-Small Cell Lung Cancer Expert Committee of the Chinese Society of Clinical Oncology (CSCO).

  
  

• Member of the Standing Committee of the Young Expert Committee of the Chinese Society of Clinical Oncology (CSCO).

  
  

• Member of the Lung Cancer Committee of the Chinese Anti-Cancer Association

• Vice Chairman of the Youth Committee of the Lung Cancer Committee of the Chinese Anti-Cancer Association

• Member of the Youth Committee of the Oncology Branch of the Chinese Medical Association

• Vice Chairman of the Cancer Chemotherapy Committee of the Association for the Promotion of Chinese Health Science and Technology

• Vice Chairman of the Lung Cancer Committee of the China Geriatric Health Care Association

• Member of the Standing Committee of the Difficult Tumor Committee of the China Medical Education Association

Treatment of ALK-positive NSCLC brain metastases is worrying, and ALK targets the emergence of a new drug, buegtinib

Lung cancer is The first malignant tumor in China's morbidity and mortality ¹, and patients with brain metastases have a poor prognosis, the natural average survival time is only 1-2 months, and the quality of life will be greatly reduced, brain metastases may bring very painful nervous system-related symptoms, such as headache, vomiting, optic nerve papilledema and other symptoms of increased intracranial pressure, and may also appear mental abnormalities, seizures, movement disorders, sensory disorders, aphasia, visual impairment and other neurocentric symptoms ²

With the advancement of medical science and technology and the update of technical concepts, the treatment of ALK-positive patients with advanced NSCLC has gradually become precise and long-term survival

Professor Wang Zhijie said that for patients with ALK-positive advanced stages, the previous ALK-TKI has improved compared with the intracranial benefits of chemotherapy, but a generation of ALK-TKI cannot penetrate the blood-brain barrier due to the molecular structure of the substrate, and it is difficult to achieve effective blood concentrations in the skull, so the control of brain metastasis is still not ideal and still cannot meet the needs

Table 1: ALTA-1L findings

Figure 1: Alta-1L study of brain metastases subgroup PFS results

Better survival, the first ALK-TKI to achieve significant benefits in survival and quality of life

In addition to drug efficacy, safety and quality of life are also of concern, especially for patients with cerebral metastases, who pay more attention to
intracranial cognitive and emotional function.

The results of the ALTA-1L study showed that bogetinib benefited significantly from patients' quality of life and had a better
safety profile.

Professor Wang Zhijie said that in terms of quality of life, the first-line treatment of bogetinib significantly improved the quality of life scale (HRQoL) to worsen the time of exacerbation of more than 18 months, and the quality of life
improved in a sustained manner.

Bugotinib significantly improved to worsening time in multiple dimensions, particularly the clinically concerned intracranial function - cognitive/affective function benefit, taking into account good intracranial symptom improvement and functional benefit; Benefits for gastrointestinal-related symptoms (nausea and vomiting, decreased appetite, constipation) help improve medication ^adherence4
.

Figure 2: EORTC-QOL-C30 score degradation time

The overall safety of bogetinib is good, the adverse events (AE) are mostly 1-2 grades, and the safety is ^{controllable3}
.

Bugotinib's good intracranial efficacy, combined with good intracranial safety, provides a new treatment option for patients with NSCLC who are ALK-positive with brain metastases
.

Multidisciplinary and accurate diagnosis and treatment will help advanced lung cancer truly achieve "chronic" development

Professor Wang Zhijie believes that a large part of the survival benefit for patients with advanced lung cancer comes from the advent of the era of precision diagnosis and treatment, and many patients have gradually transitioned from the traditional single chemotherapy to targeted therapy and immunotherapy
.

In the era of accurate diagnosis and treatment, it is necessary to apply multidisciplinary wisdom and mobilize internal medicine, surgery, radiotherapy, pathology, immunology and biological information analysis to conduct full discussion, so multidisciplinary comprehensive diagnosis and treatment involves almost all aspects
of advanced lung cancer treatment.

In the era of precision treatment, only a truly reasonable and orderly multidisciplinary diagnosis and treatment of advanced lung cancer can make the 5-year survival rate of patients continue to improve, so that advanced lung cancer can truly achieve "chronic" development
.

References:

1.
LI Caihe, HU Changchen, CHENG Dongdong,et al.
Progress in targeted therapy for brain metastasis of non-small cell lung cancer[J].
Chinese Hospital Drug Evaluation and Analysis, 2022, 22(4):7.

2.
Oncologist Branch of Chinese Medical Doctor Association, Oncology Branch of China Association for the Promotion of International Exchange in Healthcare.
Chinese Treatment Guidelines for Brain Metastases for Lung Cancer (2021 Edition)[J].
Chinese Journal of Oncology Vol.
43, No.
3, 2021, pp.
269-281.

3.
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.

4.
Camidge DR, Kim HR, Ahn MJ, et al.
Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial.
J Thorac Oncol.
2021; 16(12):2091-2108.

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.

Such information should not in any way replace professional medical guidance and should not be considered a medical advice
.

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.

Approval code: C-APROM/CN/ALUN/0253

Date of approval: August 2022

Edit: Candy

Typography: Uni

Execution: Traveller