Preface
Non-small cell lung cancer (NSCLC) is the main pathological subtype of lung cancer, and immune checkpoint inhibitors (ICIs) have brought significant survival benefits to patients with driver-negative NSCLC, but most patients still face drug resistance. At present, the second-line treatment recommendation for NSCLC in the Chinese treatment guidelines is based on the evidence of first-line platinum-containing chemotherapy, which is mainly single-agent chemotherapy or single-agent immunotherapy, and there is a lack of research data in this group of immunotherapy, and the treatment options are very limited. With the widespread application of first-line ICIs therapy, more attention has been paid to exploring cutting-edge treatment strategies.
Based on this, the Expert Committee on Non-Small Cell Lung Cancer of the Chinese Society of Clinical Oncology took the lead and organized experts in related fields, combined with the 2023 edition of the guidelines of the Chinese Society of Clinical Oncology, and referred to the latest domestic and foreign literature, clinical research data and the latest conference reports, and on the basis of the joint discussion of the expert group, the "Chinese Expert Consensus on the Second-line Treatment of Driver Gene Negative Non-Small Cell Lung Cancer" (hereinafter referred to as the "Consensus") was formulated after unifying opinions, in order to provide a reference for the second-line treatment of patients with driver gene negative NSCLC. Yimaitong invited consensus writing expert and Professor Zhou Fei of Shanghai East Hospital to interpret.
Professor Zhou Fei
- Department of Oncology, Shanghai East Hospital
- Doctor of Medicine, Deputy Chief Physician, Associate Professor, Master's Supervisor
- Member of the IASLC Global Multidisciplinary Standards Committee on Practice
- Youth Council of China Anti-Cancer Association
- Member of Thoracic Oncology Branch of China Medical Promotion Association
- Secretary of the Lung Cancer Professional Committee of the China Primary Health Care Foundation
- Youth Council of Shanghai Anti-Cancer Association
- Shanghai Shenkang Youth Post Expert
- Shanghai Young Science and Technology Talents "Sailing" Program
- Shanghai "Medical Garden Rising Star" young medical talent
- CSCO“35 under 35”“最具潜力青年肿瘤医师”、“科研达人奖”
- 《中国癌症杂志》《Cancer Drug Resistance》《Cancer Advances》青年编委
Consensus points
One
Pre-treatment evaluation
The consensus points out that the choice of second-line treatment regimen for NSCLC needs to be comprehensively evaluated according to the response to first-line therapy, whether immunotherapy has been received, the duration of first-line treatment, and the presence of autoimmune diseases.
Two
Recommendations for the clinical application of second-line drugs for driver gene-negative NSCLC
1
Recommendations for second-line treatment in non-immunotreated patients
➤ Chemotherapy or chemotherapy in combination with anti-angiogenic drugs
Patients with a PS score of 0 to 2 can be given second-line chemotherapy after progression on first-line non-immunotherapy. Two-agent chemotherapy regimens have not shown a survival benefit over single-agent chemotherapy in second-line chemotherapy, so monotherapy with docetaxel or pemetrexed is recommended. Patients who cannot tolerate chemotherapy or are unwilling to undergo chemotherapy and have a PS score of >2 may be considered for the small molecule anti-angiogenic drug anlotinib. For patients with a PS score of >2, chemotherapy is not recommended, and optimal supportive care is recommended.
➤ Immunotherapy
PD-1/PD-L1 inhibitors have become the new standard of care for second-line driver negative NSCLC. Based on the Phase III CheckMate078 study, the National Medical Products Administration (NMPA) approved nivolumab for the second-line treatment of EGFR/anaplastic lymphoma kinase (ALK)-negative or unknown stage IV NSCLC, and this consensus makes a first-level recommendation. In the RATIONALE 303 study, tislelizumab had a significant clinical benefit compared with docetaxel in second- or third-line NSCLC, with an ORR of 22.6 versus 7.1 percent and a median OS of 17.2 versus 11.9 months (HR=0.64, P<0.0001). In terms of safety, tislelizumab has a lower incidence of grade 3 TEAEs than docetaxel≥ The NMPA has approved tislelizumab for the second-line treatment of EGFR/ALK-negative or unknown stage IV NSCLC, and this consensus makes a first-class recommendation.
2
Recommendations for second-line treatment in patients treated with immunotherapy combined with chemotherapy
➤ Clinical studies for immunotherapy-experienced patients are being deployed, but no treatment regimen has been approved for use in China. Considering the response and tolerability of patients to ICIs in the first-line treatment, the follow-up research was divided into elimination, retention, and switching to ICIs: (1) elimination of ICIs: anti-angiogenic drugs combined with chemotherapy or chemotherapy were used; (2) Retention of the original ICIs: the original ICIs in combination with others (radiotherapy/chemotherapy/anti-angiogenic drugs/double immunity); (3) Switching to ICIs: Changing immunotherapy drugs can be combined with anti-angiogenic drugs and other treatments at the same time.
➤ For patients with a PS score of 0-2 after progression on first-line immunotherapy, pemetrexed monotherapy or docetaxel monotherapy can be selected (if the same drug is not used in first-line therapy). Based on the ALTER-L016 and L018 studies, this consensus recommends anlotinib in combination with docetaxel as the secondary recommendation. For patients with a PS score of >2, optimal supportive care is recommended.
3
Recommendations for second-line treatment in patients treated with immunotherapy monotherapy
➤ For first-line immunotherapy monotherapy patients [PD-L1 tumor cell positive proportion score (TPS) ≥50%], platinum-doublet chemotherapy is currently routinely recommended for second-line therapy. After progression, docetaxel or pemetrexed (non-squamous carcinoma) single-agent chemotherapy can be selected as first-line recommendations. In patients with driver-negative advanced NSCLC, anlotinib may be used as a first-tier recommendation for third-line and above treatment. In addition, participation in clinical studies is a tertiary recommendation for patients treated in the third line.
Expert interpretation
1
What do you think is the significance of the release of the Chinese Expert Consensus on the Second-Line Treatment of Driver Gene Negative Non-Small Cell Lung Cancer for clinical practice?
Professor Zhou Fei: Lung cancer is one of the malignant tumors with high morbidity and mortality in mainland China and other countries around the world, and with the development of diagnosis and treatment technology, especially after entering the era of targeted and immunotherapy, the survival of lung cancer patients has been significantly improved. Immunotherapy is particularly useful for patients with advanced NSCLC who are negative for driver genes. However, despite the success of initial treatment, patients still face disease progression or treatment failure. With the increasing use of first-line immunotherapy, the development of second-line treatment strategies for patients with driver-negative advanced NSCLC has become more complex and challenging. Based on the first-line use of immune checkpoint inhibitors, combined with the existing evidence, the "Consensus" provides a guiding basis and use norms for Chinese clinicians to select the second-line treatment of driver gene-negative NSCLC.
2
There are still many unanswered questions in the field of second-line treatment of driver gene-negative NSCLC, what efforts do you think needs to be made in this area in the future?
At present, the combination therapy of anti-angiogenic drugs and ICIs is an important strategy for the second-line treatment of driver gene-negative NSCLC, and the application prospect is broad. It is hoped that there will be more evidence from phase III clinical trials in the future to validate the feasibility of these combination therapies. In the future, drug resistance and post-biopsy will be needed to reveal the mechanism of drug resistance in immunotherapy at multiple levels such as tumor cells, tumor microenvironment, and host, so as to design relevant clinical studies to overcome drug resistance. In addition, new treatment modalities such as electric field therapy are being explored, and with the disclosure of more clinical data and research results of these new treatment modalities, it is expected to further enrich the second-line treatment strategies for driver gene-negative NSCLC in the future.
Editor: Faline
Reviewer: Prof. Fei Zhou
Typesetting: Faline
Execution: Faline
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