Abstract
Background Currently, six ALK inhibitors (including crizotinib, alectinib, ceritinib, brigatinib, ensartinib, and lorlatinib) have been approved for first-line treatment of ALK-positive advanced non-small cell lung cancer, yet clinical selection remains challenging.
Objective To comprehensively evaluate these six ALK inhibitors across five dimensions—safety, efficacy, pharmaceutical characteristics, economics, and other attributes—to provide evidence-based support for clinical decision-making.
Methods Data required for evaluation, including drug efficacy, safety, and pricing, were collected from authoritative sources from database inception to December 2024, including drug package inserts, guidelines from the National Comprehensive Cancer Network (NCCN), Chinese Society of Clinical Oncology (CSCO), and European Society for Medical Oncology (ESMO), network Meta-analyses, as well as the Zhejiang Province Medical Insurance Information Platform for Designated Medical Institutions and Pharmacies, National Medical Insurance Information Database, and Center for Drug Evaluation of the National Medical Products Administration. Based on the "Quick Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition)", the Delphi method was employed to construct a comprehensive evaluation system comprising five dimensions (safety, efficacy, pharmaceutical characteristics, economics, and other attributes) for systematic assessment of the six ALK inhibitors: crizotinib, alectinib, ceritinib, brigatinib, ensartinib, and lorlatinib. An expert panel of nine members with senior professional titles and over five years of experience in relevant fields conducted six rounds of discussions to finalize evaluation criteria (three rounds to determine evaluation items and another three rounds to allocate scores for each item). Final results were independently evaluated and statistically analyzed by a two-person team according to the established evaluation standards.
Results The comprehensive evaluation ranking of the six ALK inhibitors was: brigatinib (85.5 points) > alectinib (82.7 points) > lorlatinib (82.2 points) > ensartinib (78.8 points) > ceritinib (77.4 points) > crizotinib (76.5 points). Alectinib was optimal in the core dimensions (safety/efficacy/pharmaceutical characteristics) with 71.0 points. Generational trend evaluation revealed: second generation > third generation > first generation (except for ceritinib/ensartinib); core dimension generational trend evaluation showed: third generation > second generation > first generation (except for alectinib/ceritinib).
Conclusion This study confirms that different ALK inhibitors possess distinct advantages across the five dimensions of efficacy, safety, pharmaceutical characteristics, economics, and other attributes. Brigatinib achieved higher comprehensive scores than other ALK inhibitors, while alectinib scored highest in core dimensions. Second- and third-generation drugs demonstrated superior overall performance. These evaluation results can provide important references for medical institutions to select individualized treatment regimens based on clinical needs.
Full Text
Comprehensive Evaluation of ALK Inhibitors in First-Line Treatment for ALK-Positive Advanced Non-Small Cell Lung Cancer
YE Ziqi, ZHOU Yujun, LIU Liu, ZHANG Yanfang, HONG Yun, RAO Yuefeng*
Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
Corresponding author: RAO Yuefeng, Chief Pharmacist/Doctoral Supervisor; E-mail: raoyf@zju.edu.cn
Abstract
Background: Currently, six ALK inhibitors (crizotinib, alectinib, ceritinib, brigatinib, ensartinib, and lorlatinib) are approved for first-line treatment of ALK-positive advanced non-small cell lung cancer (NSCLC), yet clinical decision-making remains challenging. Objective: This study comprehensively evaluated these six ALK inhibitors across five dimensions—safety, efficacy, pharmaceutical properties, economy, and other attributes—to provide evidence-based support for clinical drug selection. Methods: Data from database inception through December 2024 were collected from drug labels, guidelines by the National Comprehensive Cancer Network (NCCN), Chinese Society of Clinical Oncology (CSCO), and European Society for Medical Oncology (ESMO), network meta-analyses, and authoritative platforms including the Zhejiang Provincial Two-Designated Healthcare Security Information Database, National Healthcare Security Administration Information Database, and National Medical Products Administration Drug Evaluation Center. Based on the Rapid Guideline for Drug Evaluation and Selection in Chinese Medical Institutions (2nd Edition), a comprehensive evaluation system comprising five dimensions was developed using the Delphi method to assess all six ALK inhibitors. A nine-member expert panel with senior professional titles and over five years of relevant experience conducted six discussion rounds to finalize evaluation criteria (three rounds to define items and three to assign weights). Final scoring was performed independently by a two-researcher team according to established standards, with third-party expert arbitration for significant discrepancies.
Results: The overall ranking was: brigatinib (85.5 points) > alectinib (82.7 points) > lorlatinib (82.2 points) > ensartinib (78.8 points) > ceritinib (77.4 points) > crizotinib (76.5 points). Alectinib scored highest in core dimensions (safety/efficacy/pharmaceutical properties) with 71.0 points. Generational trend analysis showed second-generation inhibitors outperformed third- and first-generation drugs (except ceritinib/ensartinib), while third-generation inhibitors ranked highest in core dimensions (except alectinib/ceritinib). Conclusion: This study demonstrates that different ALK inhibitors exhibit distinct advantages across the five evaluated dimensions. Brigatinib achieved the highest overall score, while alectinib ranked highest in core dimensions. Second- and third-generation drugs generally performed better, providing valuable evidence for individualized treatment selection based on clinical needs.
Keywords: ALK inhibitors; Non-small cell lung cancer; Comprehensive evaluation; Clinical rational drug use; Individualized treatment
Introduction
Lung cancer ranks among the most prevalent and lethal malignant tumors worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 80% of all lung cancer cases. ALK-positive NSCLC represents 3%–7% of NSCLC cases [1]. Over the past two decades, the treatment paradigm for NSCLC has shifted from traditional cytotoxic chemotherapy to precision targeted therapy. Molecular targeted therapy for driver mutations has become the standard of care for advanced NSCLC patients harboring actionable alterations due to its superior efficacy and safety profile. The ALK gene serves as a key driver in NSCLC, with activation mechanisms primarily including chromosomal rearrangement-induced fusion, gene amplification, and point mutations [2]. Small-molecule tyrosine kinase inhibitors (TKIs) targeting ALK fusion have demonstrated clinical success, with six ALK inhibitors (crizotinib, alectinib, ceritinib, brigatinib, ensartinib, and lorlatinib) currently approved for first-line treatment of advanced ALK-positive NSCLC [3]. However, this multiplicity of first-line options presents significant challenges for clinical decision-making.
Previous studies have systematically evaluated these six ALK inhibitors [4], but most relied on pairwise meta-analyses and descriptive comparisons, introducing inherent bias risks and limiting clinical applicability due to the lack of direct comparative evidence. This study constructed an evaluation framework based on the Rapid Guideline for Drug Evaluation and Selection in Chinese Medical Institutions (2nd Edition) [5] and validated it through a rigorous Delphi process to conduct a comprehensive clinical evaluation of ALK inhibitors, providing evidence-based guidance for drug selection and formulary decisions in healthcare institutions.
1. Materials and Methods
1.1 Data Collection
Data from database inception through December 2024 were collected from drug labels (crizotinib: Pfizer Investment Co., Ltd.; alectinib: Shanghai Roche Pharmaceuticals Ltd.; ceritinib: Beijing Novartis Pharmaceutical Co., Ltd.; brigatinib: Takeda [China] International Trading Co., Ltd.; ensartinib: Betta Pharmaceuticals Co., Ltd.; lorlatinib: Pfizer Investment Co., Ltd.), the NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer (2024.V4) [6], CSCO Guidelines for Diagnosis and Treatment of Non-Small Cell Lung Cancer (2024 Edition) [7], ESMO Clinical Practice Guidelines for Metastatic Non-Small Cell Lung Cancer (2023 Edition) [8], network meta-analysis by Ma et al. [9], and authoritative databases including the Zhejiang Provincial Two-Designated Healthcare Security Information Platform (https://med.ybj.zj.gov.cn), National Healthcare Security Information Database (https://code.nhsa.gov.cn), and National Medical Products Administration Drug Evaluation Center (https://www.cde.org.cn). Clinical trials were included if they reported at least one primary endpoint (overall survival [OS] or objective response rate [ORR]), were randomized controlled trials (RCTs) in English or Chinese, and excluded case reports, studies with sample sizes <50, or those without control groups. Two researchers independently extracted data.
1.2 Drugs Included in Evaluation
Six ALK inhibitors approved for first-line treatment of advanced ALK-positive NSCLC in China were evaluated: crizotinib, ceritinib, alectinib, brigatinib, ensartinib, and lorlatinib. Except for crizotinib, no generic or centralized procurement versions are currently available. As all clinical trials were conducted with original drugs, this evaluation included six original drugs for comprehensive assessment.
1.3 Evaluation Method
Based on the Rapid Guideline for Drug Evaluation and Selection in Chinese Medical Institutions (2nd Edition) [5], which employs Mini-Health Technology Assessment (Mini-HTA) combined with the System of Objectified Judgement Analysis (SOJA), we constructed a five-dimensional evaluation system covering pharmaceutical properties, efficacy, safety, economy, and other attributes. Pharmaceutical properties, efficacy, and safety constitute the three core dimensions, with weights determined by the steering committee and expert panel through Delphi method. For specific scoring criteria and items not explicitly defined in the guideline (e.g., scoring for specific drugs on primary outcomes), a nine-member expert panel was convened, comprising three medical oncologists, three pharmacists, two health economists, and one evidence-based medicine specialist, all with senior professional titles and over five years of relevant experience. The Delphi process involved:
Phase 1: Item Determination (3 rounds)
- Round 1: Define core dimensions
- Round 2: Define specific items under each core dimension
- Round 3: Confirm the evaluation indicator list
Phase 2: Score Allocation (3 rounds)
- Round 1: Independent anonymous scoring by experts
- Round 2: Consensus meeting to discuss controversial criteria
- Round 3: Rescoring based on revised criteria until >80% agreement was achieved
Two researchers independently evaluated the six ALK inhibitors using the validated criteria. Third-party expert arbitration was sought for significant discrepancies, with final results determined through discussion.
1.4 Evaluation Indicators
The evaluation system comprised five dimensions:
1.4.1 Efficacy (Total: 27 points)
- Indication (5 points): First-line recommendation in NCCN, ESMO, and CSCO guidelines (5 points); second-line (3 points); optional (1 point)
- Guideline Recommendation (12 points): Level I recommendation (Class A evidence: 12 points; Class B: 11 points; Class C and others: 10 points); Level II recommendation (Class A: 9 points; Class B: 8 points; Class C and others: 7 points); expert consensus recommendation (society-organized, systematic review-based: 6 points; society-organized: 5 points; others: 4 points); systematic review/meta-analysis (large sample/high quality: 3 points; small sample/low quality: 2 points; non-RCT systematic review: 1 point)
- Clinical Efficacy (10 points): Based on Ma et al.'s network meta-analysis [9], with progression-free survival (PFS) as primary endpoint and ORR as secondary endpoint. For PFS, the best-performing drug received 6 points, with others scored in 0.2-point decrements; for ORR, the best received 4 points, with others in 0.2-point decrements
1.4.2 Safety (Total: 25 points)
- Adverse Drug Reactions (ADRs) (8 points):
- Moderate ADRs (CTCAE Grades 1-2): Based on Ma et al. [9], lowest incidence received 3 points, others in 0.2-point decrements
- Severe ADRs (CTCAE Grades 3-4): Lowest incidence received 5 points, others in 0.2-point decrements
- Special Populations (11 points): Pediatric use (2 points), geriatric use (1 point), pregnancy (1 point), lactation (1 point), hepatic impairment (3 points), renal impairment (3 points)
- ADR from Drug Interactions (3 points): No dose adjustment needed (3 points); dose adjustment required (2 points); concomitant use prohibited (1 point)
- Other Safety Factors (3 points): Reversible ADRs (1 point), no teratogenicity/carcinogenicity (1 point), no special warnings (1 point)
1.4.3 Pharmaceutical Properties (Total: 28 points)
- Pharmacology (5 points): Definite clinical efficacy, clear mechanism, innovative target (5 points); definite efficacy, clear mechanism (4 points); moderate efficacy, unclear mechanism (2 points); general efficacy, unclear mechanism (1 point)
- Pharmacokinetics (5 points): Clear PK profile with complete parameters (5 points); clear profile with incomplete parameters (3 points); unclear profile or no PK studies (1 point)
- Pharmaceutics and Administration (12 points): Active ingredients and excipients (2 points), specifications/packaging (2 points), dosage form (2 points), dosing regimen (2 points), dosing frequency (2 points), ease of use (2 points)
- Storage Conditions (4 points): Ambient temperature storage (3 points), cool storage (2 points), refrigeration/freezing (1 point); no light protection needed (1 point)
- Shelf Life (2 points): ≥60 months (2 points); ≥36 to <60 months (1.5 points); ≥24 to <36 months (1 point); ≥12 to <24 months (0.5 points); <12 months (0.25 points)
1.4.4 Economy (Total: 10 points)
Based on average daily treatment cost comparison. The drug with lowest daily cost received 10 points; others scored as (lowest daily cost / evaluated drug's daily cost) × 7.
1.4.5 Other Attributes (Total: 10 points)
- National Reimbursement Drug List (2024) inclusion (3 points): Category A without restrictions (3 points); Category A with restrictions (2.5 points); Category B without restrictions (2 points); Category B with restrictions (1.5 points); not listed (1 point)
- National Essential Medicines List (2018) inclusion (3 points): Essential medicine without special requirements (3 points); essential medicine with requirements (2 points); non-essential (1 point)
- National Centralized Procurement (1 point): Included (1 point); not included (0 points)
- Consistency Evaluation (1 point): Original/reference drug (1 point); generic passing consistency evaluation (0.5 points)
- Manufacturer Status (1 point): Top 50 global pharmaceutical companies in 2024 (1 point); others (0 points)
- Global Availability (1 point): Marketed both domestically and internationally (1 point); domestic only (0 points)
2. Results
2.1 Efficacy Evaluation
2.1.1 Indications: All six ALK inhibitors are approved for ALK-positive advanced NSCLC, but guideline recommendations vary. The NCCN Guidelines (2024.V4) [6] recommend five ALK inhibitors (crizotinib, ceritinib, alectinib, brigatinib, lorlatinib). The ESMO Guidelines (2023 Edition) [8] recommend the same five, with alectinib, brigatinib, and lorlatinib as preferred options. The CSCO Guidelines (2024 Edition) [7] recommend all six, with alectinib as the optimal choice. Therefore, alectinib, brigatinib, and lorlatinib received 5 points; crizotinib and ceritinib received 3 points; ensartinib received 1 point.
2.1.2 Guideline Recommendations: All six ALK inhibitors received Level I recommendation (Class 1A evidence) in the CSCO Guidelines (2024 Edition) [7], earning 12 points each.
2.1.3 Clinical Efficacy: Based on Ma et al.'s network meta-analysis [9], PFS and ORR rankings were:
- PFS: lorlatinib (6 points) > alectinib (5.8) > ensartinib (5.6) > brigatinib (5.4) > crizotinib (5.2) > ceritinib (5.0)
- ORR: alectinib (4 points) > lorlatinib (3.8) > brigatinib (3.6) > ensartinib (3.4) > ceritinib (3.2) > crizotinib (3.0)
Overall Efficacy Scores: Alectinib and lorlatinib (26.8 points each) > brigatinib (26.0) > ensartinib (24.0) > crizotinib and ceritinib (23.2 each)
2.2 Safety Evaluation
2.2.1 ADRs: Based on Ma et al. [9]:
- Moderate ADRs: crizotinib (3 points) > brigatinib and lorlatinib (2.8 each) > ceritinib and ensartinib (2.6 each) > alectinib (2.4)
- Severe ADRs: alectinib (5 points) > crizotinib (4.8) > brigatinib (4.6) > ensartinib (4.4) > lorlatinib (4.2) > ceritinib (4.0)
- ADR Composite Score: Crizotinib (7.8) > alectinib and brigatinib (7.4 each) > lorlatinib and ensartinib (7.0 each) > ceritinib (6.6)
2.2.2 Special Populations: None of the six ALK inhibitors are approved for children, pregnant, or lactating women. All are usable in elderly patients and require no dose adjustment for hepatic or renal impairment. All six drugs received 7 points in this category [TABLE:1].
2.2.3 Drug Interaction-Related ADRs: Alectinib and ensartinib require no dose adjustment when interacting drugs are co-administered (3 points). Brigatinib requires dose adjustment (2 points). Lorlatinib, ceritinib, and crizotinib prohibit concomitant use with interacting drugs (1 point each).
2.2.4 Other Safety Factors: All ADRs are reversible (1 point each). No teratogenicity or carcinogenicity has been reported (1 point each). Crizotinib carries warnings for heart failure and visual loss in pediatric patients (0 points), while alectinib, ceritinib, lorlatinib, brigatinib, and ensartinib have no special warnings (1 point each).
Overall Safety Scores: Alectinib (18.4) > ensartinib (18.0) > brigatinib (17.4) > lorlatinib (16.0) > crizotinib (15.8) > ceritinib (15.6)
2.3 Pharmaceutical Properties Evaluation
2.3.1 Pharmacology: All six ALK inhibitors demonstrate definite efficacy with clear mechanisms. For innovation: crizotinib (first-generation) scored 4.6; ceritinib, alectinib, ensartinib, and brigatinib (second-generation) scored 4.8 each; lorlatinib (third-generation) scored 5.0.
2.3.2 Pharmacokinetics: Crizotinib, alectinib, and lorlatinib have complete PK parameters in their labels (5 points each). Ceritinib (lacking relative bioavailability, Cmax, and AUC), ensartinib (lacking relative bioavailability), and brigatinib (lacking relative bioavailability) have incomplete PK data (3 points each) [TABLE:2].
2.3.3 Pharmaceutics and Administration:
- Ingredients: Ensartinib did not list excipients (1 point); the other five had complete information (2 points each)
- Specifications: All six are suitable for clinical use and dose adjustment (2 points each)
- Dosage Form: All are oral formulations (2 points each)
- Dosing Frequency: Crizotinib and alectinib require twice-daily dosing (1.5 points each); ceritinib, ensartinib, brigatinib, and lorlatinib are once-daily (2 points each)
- Ease of Use: All six can be self-administered (2 points each) [TABLE:3]
2.3.4 Storage Conditions: All six ALK inhibitors can be stored at ambient temperature (3 points each) [TABLE:3].
2.3.5 Shelf Life: Ceritinib and ensartinib have 24-month shelf lives (1 point each); the other four have 36-month shelf lives (1.5 points each) [TABLE:3].
Overall Pharmaceutical Properties Scores: Lorlatinib (27.5) > brigatinib (26.8) > alectinib (25.8) > ceritinib and ensartinib (24.8 each) > crizotinib (24.6)
2.4 Economy Evaluation
Based on average daily treatment costs: brigatinib (10 points) > ensartinib (8.5) > ceritinib (8.3) > crizotinib (7.4) > lorlatinib (6.4) > alectinib (6.2) [TABLE:4].
2.5 Other Attributes Evaluation
Other attributes included reimbursement status, essential medicine listing, centralized procurement, original drug status, international availability, and manufacturer ranking. Composite scores: crizotinib, ceritinib, alectinib, and lorlatinib (5.5 points each) > brigatinib (5.3) > ensartinib (3.5) [TABLE:5].
2.6 Overall Composite Scores
The final comprehensive ranking was: brigatinib (85.5 points) > alectinib (82.7) > lorlatinib (82.2) > ensartinib (78.8) > ceritinib (77.4) > crizotinib (76.5). Alectinib scored highest in core dimensions (safety/efficacy/pharmaceutical properties) with 71.0 points [TABLE:6].
2.7 Generational Analysis
Generational classification: first-generation (crizotinib), second-generation (ceritinib, alectinib, ensartinib, brigatinib), third-generation (lorlatinib). Trends revealed:
- Efficacy: Third-generation (lorlatinib 26.8) > second-generation (ensartinib 24.0, brigatinib 26.0) > first-generation (crizotinib 23.2) (except alectinib/ceritinib)
- Safety: Second-generation (alectinib 18.4, ensartinib 18.0, brigatinib 17.4) > third-generation (lorlatinib 16.0) > first-generation (crizotinib 15.8) (except ceritinib)
- Pharmaceutical Properties: Third-generation (lorlatinib 27.5) > second-generation (ceritinib 24.8, alectinib 25.8, ensartinib 24.8, brigatinib 26.8) > first-generation (crizotinib 24.6)
- Economy: Second-generation (ceritinib 8.3, ensartinib 8.5, brigatinib 10.0) > first-generation (crizotinib 7.4) > third-generation (lorlatinib 6.4) (except alectinib)
- Other Attributes: Minimal generational differences (except ensartinib)
Overall generational trends: second-generation (alectinib 82.7, brigatinib 85.5) > third-generation (lorlatinib 82.2) > first-generation (crizotinib 76.5) (except ceritinib/ensartinib). Core dimension trends: third-generation (lorlatinib 70.3) > second-generation (ensartinib 66.8, brigatinib 70.2) > first-generation (crizotinib 63.6) (except alectinib/ceritinib) [TABLE:6].
Discussion
First-line targeted therapy for ALK-positive advanced NSCLC has advanced significantly, with six original ALK inhibitors now approved in China and recommended by NCCN, ESMO, and CSCO guidelines. However, selecting the optimal drug remains challenging, particularly regarding intergenerational differences in efficacy, safety, and economy. This study established a five-dimensional evaluation system to provide evidence-based guidance for clinical decision-making. Brigatinib achieved the highest overall score (85.5), while alectinib ranked highest in core dimensions (71.0), offering crucial insights for personalized therapy.
The scoring system enables quantitative ranking across multiple dimensions, providing objective evidence for clinical practice. Specifically: alectinib led in the composite core dimension score (safety/efficacy/pharmaceutical properties); alectinib and lorlatinib ranked highest in efficacy alone; lorlatinib led in pharmaceutical properties; alectinib led in safety; brigatinib led in economy; and crizotinib, ceritinib, alectinib, and lorlatinib led in other attributes. Generational analysis revealed third-generation drugs' superiority in efficacy, pharmaceutical properties, and other attributes, with particular advantages against brain metastases and resistant mutations (e.g., G1202R) [12]. Second-generation drugs demonstrated better safety and economic profiles. Notably, given that 35–50% of ALK-positive NSCLC patients develop brain metastases [13], second- and third-generation drugs' superior blood-brain barrier penetration significantly improves central nervous system disease control [14], with lorlatinib showing particular efficacy against leptomeningeal metastases [15].
While previous evaluations of ALK inhibitors exist [4], this study offers methodological innovations: (1) strict adherence to the Rapid Guideline for Drug Evaluation and Selection (2nd Edition) [5] with structured Delphi validation by a multidisciplinary expert panel, ensuring methodological rigor and clinical relevance; (2) development of a systematic framework integrating multidimensional indicators tailored for first-line ALK-positive NSCLC treatment; (3) creation of a Delphi-validated scoring system with enhanced practicality for clinical decision-making.
These findings apply to first-line treatment decisions for ALK-positive advanced NSCLC, particularly for: (1) high brain metastasis burden—prioritize third-generation drugs (lorlatinib); (2) economic constraints—prioritize second-generation drugs (e.g., brigatinib); (3) resistant mutations—third-generation drugs remain effective against G1202R and similar mutations. The six evaluated ALK inhibitors have maintained stable core indications since approval, and by strictly focusing on the first-line setting, this study avoided confounding factors from later-line or off-label use, ensuring result reliability. Although drug pricing fluctuates, all six ALK inhibitors have been included in China's National Reimbursement Drug List [10] through national negotiation, providing relatively stable cost structures. A dynamic update mechanism was designed for long-term validity: (1) modular system design allows independent updates for single variables (e.g., price changes, new safety data) without reconstructing the entire framework; (2) regular monitoring will track policy changes and update data in subsequent studies.
This study has limitations: (1) the expert-based scoring system, though rigorously validated, carries inherent subjectivity; (2) efficacy evaluation relies on network meta-analysis data, potentially introducing bias due to the lack of head-to-head trials; (3) using PFS as the primary endpoint requires caution as immature OS data may affect final efficacy assessment; (4) safety data from network meta-analyses may carry potential bias in ADR incidence evaluation; (5) results reflect current evidence levels and require dynamic updating as labels, guidelines, and prices evolve; (6) the study did not cover later-line therapy or special populations (e.g., hepatic impairment), requiring individualized assessment. These factors necessitate careful interpretation and integration of latest evidence when applying these conclusions.
In summary, this study innovatively integrated multidimensional evidence with expert consensus to establish a comprehensive ALK inhibitor evaluation system, providing important reference for clinical practice, personalized treatment decisions, and health policy adjustments.
Author Contributions
YE Ziqi: literature search, guideline review, and initial manuscript drafting. ZHOU Yujun, LIU Liu, ZHANG Yanfang, and HONG Yun: data collection and organization. RAO Yuefeng: quality control, manuscript review, supervision of the entire research process, and revision.
Conflict of Interest
The authors declare no conflict of interest.
References
[1] ADDEA A, TABBO F, ROBINSON T, et al. Precision Medicine in ALK Rearranged NSCLC: A Rapidly Evolving Scenario [J]. Crit Rev Oncol Hematol, 2018, 122:150-156. DOI:10.1016/j.critrevonc.2017.12.015.
[2] BAYLISS R, CHOI J, FENNELL D A, et al. Molecular mechanisms that underpin EML4-ALK driven cancers and their response to targeted drugs [J]. Cell Mol Life Sci, 2016, 73(6):1209-1224. DOI:10.1007/s00018-015-2117-6.
[3] PENG L, ZHU L P, SUN Y L, et al. Targeting ALK rearrangements in NSCLC: current state of the art [J]. Front Oncol, 2022, 12:863461. DOI:10.3389/fonc.2022.863461.
[4] WANG W Q, XU T, ZHANG J J, et al. A comprehensive clinical evaluation of first-line drugs for ALK-positive advanced non-small cell lung cancer [J]. J Thorac Dis, 2023, 15(4):1935-1947. DOI:10.21037/jtd-23-380.
[5] ZHAO Zhigang, DONG Zhanjun, LIU Jianping. Rapid Guideline for Drug Evaluation and Selection in Chinese Medical Institutions (2nd Edition) [J]. Herald of Medicine, 2023, 42(4):447-456. DOI:10.3870/j.issn.1004-0781.2023.04.001.
[6] RIELY G J, WOOD D E, ETZINGER D S, et al. Non-small cell lung cancer, version 4.2024, NCCN clinical practice guidelines in oncology [J]. J Natl Compr Canc Netw, 2024, 22(4):249-274. DOI:10.6004/jnccn.2204.0023.
[7] Chinese Society of Clinical Oncology Guidelines Working Committee. CSCO Guidelines for Diagnosis and Treatment of Non-Small Cell Lung Cancer-2024 [M]. Beijing: People's Medical Publishing House, 2024:1-112.
[8] HENDRIKS L E, KERR K M, MENIS J, et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up [J]. Ann Oncol, 2023, 34(4):339-357. DOI:10.1016/j.annonc.2022.12.009.
[9] MA H C, LIU Y H, DING K L, et al. Comparative efficacy and safety of first-line treatments for advanced non-small cell lung cancer with ALK-rearranged: a meta-analysis of clinical trials [J]. BMC Cancer, 2021, 21(1):1278. DOI:10.1186/s12885-021-08879-9.
[10] National Healthcare Security Administration, Ministry of Human Resources and Social Security. Notice on Issuing the National Reimbursement Drug List (2024 Edition) [A/OL]. (2024-11-27)[2025-04-01]. https://www.gov.cn/zhengce/zhengceku/202411/content_6989859.htm.
[11] Notice on Issuing the National Essential Medicines List (2018 Edition) [A/OL]. (2018-09-30)[2025-04-01]. https://www.gov.cn/zhengce/zhengceku/2018-12/31/content_5435470.htm.
[12] SETO T, HAYASHI H, SATOUCHI M, et al. Lorlatinib in previously treated anaplastic lymphoma kinase-rearranged non-small cell lung cancer: Japanese subgroup analysis of a global study [J]. Cancer Sci, 2020, 111(10):3726-3738. DOI:10.1111/cas.14576.
[13] WEICKHARDT A J, SCHEIER B, BURKE J M, et al. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer [J]. J Thorac Oncol, 2012, 7(12):1807-1814. DOI:10.1097/JTO.0b013e3182745948.
[14] CACCESE M, FERRARA R, PILOTTO S, et al. Current and developing therapies for the treatment of non-small cell lung cancer with ALK abnormalities: update and perspectives for clinical practice [J]. Expert Opin Pharmacother, 2016, 17(17):2253-2266. DOI:10.1080/14656566.2016.1242578.
[15] GEZELIUS E, PLANCK M, HAZEM B, et al. Intrathecal pemetrexed for leptomeningeal metastases in a patient with ALK-rearranged lung adenocarcinoma: a case report [J]. Cancer Chemother Pharmacol, 2024, 95(1):6. DOI:10.1007/s00280-024-04735-8.
Received: 2025-04-01; Revised: 2025-07-17