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*For medical professionals only
Grasp the trend of the guide and closely integrate practice!
In particular, the extensive-stage SCLC with a high degree of malignancy, rapid progression and very poor prognosis of patients is mainly treated with traditional chemotherapy for a long time [1].
However, in recent years, immunotherapy has made important progress in a number of clinical studies, making the immuno+ chemotherapy regimen gradually become the first-line standard of care for extensive-stage SCLC [1].
What can reflect this trend of treatment landscape is undoubtedly an update
of authoritative guidelines or consensus in the field.
In the guidelines for the diagnosis and treatment of small cell lung cancer issued by the Chinese Society of Clinical Oncology (CSCO) in 2022 (hereinafter referred to as the 2022 version of the CSCO guidelines) [2], the diagnosis and treatment recommendations for extensive-stage SCLC are mainly based on the trend of immunotherapy
.
This article will introduce
the changes in the diagnosis and treatment of SCLC in combination with the key points of the 2022 CSCO guideline update.
The premise of pathological diagnosis to standardize the treatment of cancer is to make an accurate and clear diagnosis
.
Therefore, before introducing the update of the treatment section, it is also necessary to mention the update
of the 2022 edition of the CSCO guidelines in the diagnosis section.
Compared with the 2021 version of the guidelines, the two parts of the 2022 version of the guidelines have not been adjusted, and the updates mainly focus on the "pathological diagnosis" part [2].
The update of the 2022 CSCO guidelines is mainly in response to the latest classification of lung neuroendocrine tumors proposed in the 5th edition of the classification of thoracic tumors published by the World Health Organization (WHO) in 2021 [3] (see Table 1).
Clinically diagnosed SCLC mainly corresponds to small cell carcinoma in neuroendocrine carcinoma, but it also needs to be differentiated
from other types of lung neuroendocrine tumors.
Table 1.
The 2021 edition of the WHO classification of pulmonary neuroendocrine tumors [3] The 2022 edition of the CSCO guidelines make the following level I recommendations on the morphology (routine HE staining) part of pathological diagnosis [2]
：
According to the 2021 WHO classification of neuroendocrine tumors of lung cancer; Tumor cell diameter less than 3 quiescent lymphocytes, round, oval or spindle-shaped, chromatin fine granular, no nucleoli/inconspicuous, less cytoplasm or nucleus, cell boundaries are not clear, necrosis obvious; Small cell lung cancer requires further immunohistochemistry to confirm the diagnosis
.
In addition, in the principles for the diagnosis of tissue specimens, the 2022 edition of the CSCO guidelines adds the following 3 notes [2]:
- Note 3: According to the 2021 edition of the WHO classification standards, pulmonary neuroendocrine tumors rely solely on morphology, classified according to nuclear fission image and necrosis, Ki-67 positive index can not be used to distinguish typical carcinoid and atypical carcinoid, but it is recommended to add Ki-67 detection in small biopsy specimens, which helps oncologists make treatment decisions, and helps distinguish between atypical carcinoid and high-grade neuroendocrine carcinoma, and can avoid carcinoid tumors with mechanical damage.
Atypical carcinoid diagnosis is SCLC
. - Note 4: When performing a nuclear fission count, the region with the most and split images should be counted (/2mm2), which should be a clear nuclear fission image, and if the value is near the threshold, three 2mm2 regions should be selected for counting, and finally the average number
should be reported. - Note 9: Recent studies have shown significant molecular level heterogeneity in small cell lung cancer
.
For example, TP53 and RB1 biallele inactivation, Notch signaling pathway changes, somatic gene copy number variation, etc
.
In addition, based on the molecular typing concept of lineage-defining transcription factors, SCLC is divided into four molecular subtypes (SCLC-A, -N, -P-Y) according to the high expression of ASCL1, NEUROD1, YAP1 and POU2F3 [4].
SCLC-A and SCLC-N are neuroendocrine phenotypes, with high expression of neuroendocrine differentiation driver genes INSM1 and TTF-1.
SCLC-P and SCLC-Y subtypes are non-neuroendocrine phenotypes, with activation of epithelial-mesenchymal transition, NOTCH, HIPPO signaling pathways
, etc.
In vitro experimental studies and some small sample clinical trials have observed different therapeutic sensitivities of different molecular subtypes
.
With the deepening of the understanding of SCLC heterogeneity, it is possible to practice clinical emerging therapies
guided by molecular biology in the future.
In the 2022 edition of CSCO guidelines, the initial treatment of extensive-stage SCLC
is still stratified according to whether there are local symptoms and brain metastases, and different treatment strategies
are recommended according to the patient's physical condition score (ECOG PS score).
。 Among them, for patients without local symptoms and no brain metastases, the level I recommended regimens of the 2022 version of the CSCO guidelines are mainly two categories, namely chemotherapy + immunotherapy or chemotherapy alone, of which the chemotherapy alone regimen recommendation remains unchanged [2].
In the chemotherapy + immunotherapy regimen, atezolizumab + etopolin + carboplatin maintenance regimen after 4 cycles of atezolizumab received a level I recommendation, which remains unchanged from the 2021 CSCO guidelines [2].
Based on the results of the IMpower133 study [5], the National Medical Products Administration (NMPA) approved atezolizumab in combination with chemotherapy in February 2020 for the indication of first-line treatment of extensive-stage SCLC
.
In addition, the 2022 CSCO guidelines upgrade the maintenance regimen of durvalumab + etoposide + carboplatin or cisplatin after 4 cycles to a level I recommendation (preferred, class 1A evidence) from the previous recommendation of level III (preferred, class 1A evidence) [2].
Based on the excellent performance of durvalumab in the CASPIAN study [6,7], the NMPA officially approved the indication of durvalumab combined with chemotherapy for the first-line treatment of extensive-stage SCLC in July 2021
.
The 2022 version of the CSCO guidelines also adds serplulimab + etoposide + carboplatin 4-cycle serplulimab maintenance therapy to the level III recommendation [2], which is mainly based on the results of the ASTRUM-005 study [8], but this regimen has not yet been approved for indications
in China.
In addition, the 2022 edition of the CSCO guidelines also includes a number of ongoing clinical phase III studies (such as the JUPITER028 study) for the first-line treatment of SCLC as a supplement to guideline recommendations or notes [2].
Preventive treatment
of myelosuppression The 2022 CSCO guidelines also add supportive care for myelosuppression, namely the level II recommendation (class 2A evidence) to prophylactic traracillide or granulocyte colony-stimulating factor (G-CSF) when platinum-containing ± immune checkpoint inhibitors are used in the first-line treatment of broad-stage SCLC to reduce the incidence of chemotherapy-induced myelosuppression, and similar recommendations are made in relapsed SCLC [2].
Traracillide is a CDK4/6 inhibitor that induces temporary stasis in the G1 phase of hematopoietic stem/progenitor cells (HSPCs) and lymphocytes, reducing DNA damage and apoptosis after exposure to chemotherapy, and reducing damage to bone marrow cells by chemotherapy drugs
.
The recommendation of the 2022 CSCO guidelines is based on two randomized controlled clinical studies of first-line treatment of extensive-phase SCLC (G1T28-02, G1T28-05) in which triracillide participated [9,10].
In studies, traracelib significantly reduced the incidence of neutropenia, anemia and thrombocytopenia compared with placebo, and the relevant indications have been officially approved
by the NMPA.
small
knot
In general, the update of the 2022 edition of the CSCO guidelines for the diagnosis and treatment of small cell lung cancer mainly focuses on the treatment of extensive-stage SCLC, especially the recommended upgrade
of chemotherapy + immunotherapy regimen for first-line therapy.
The atezolizumab + chemotherapy regimen and the durvalumab + chemotherapy regimen have both been recommended at level I, marking the further recognition of the clear clinical benefits of immunotherapy, and also reflecting the latest trend of drug indication approval, which is of great significance
to guide the clinical diagnosis and treatment practice of SCLC.
References:
[1] Rudin CM,Brambilla E,Faivre-Finn C,et al.
Small-cell lung cancer[J].
Nat Rev Dis Primers.
2021 Jan 14; 7(1):3.
[2] Chinese Society of Clinical Oncology Guidelines Working Committee.
Guidelines for the diagnosis and treatment of small cell lung cancer of the Chinese Society of Clinical Oncology (CSCO) 2022[M].
Beijing:People's Medical Publishing House,2022.
[3] Rekhtman N.
Lung neuroendocrine neoplasms:Recent progress and persistent challenges[J].
Modern Pathology,2022,35(1):36-50.
[4] Rudin C M,Poirier J T,Byers L A,et al.
Molecular subtypes of small cell lung cancer:a synthesis of human and mouse model data[J].
Nature Reviews Cancer,2019,19(5):289-297.
[5] Horn L,Mansfield A S,Szczęsna A,et al.
First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer[J].
New England Journal of Medicine,2018,379(23):2220-2229.
[6] Paz-Ares L,Dvorkin M,Chen Y,et al.
Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer(CASPIAN):a randomised,controlled,open-label,phase 3 trial[J].
The Lancet,2019,394(10212):1929-1939.
[7] Paz-Ares L,Chen Y,Reinmuth N,et al.
Durvalumab,with or without tremelimumab,plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer:3-year overall survival update from CASPIAN[J].
ESMO Open,2022,7(2):100408.
[8] Cheng Y,Han L,Wu L,et al.
Effect of first-line serplulimab vs placebo added to chemotherapy on survival in patients with extensive-stage small cell lung cancer:the ASTRUM-005 randomized clinical trial[J].
JAMA,2022,328(12):1223-1232.
[9] Daniel D,Kuchava V,Bondarenko I,et al.
Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive‐stage small cell lung cancer:a multicentre,randomised,double‐blind,placebo‐controlled phase II trial[J].
International Journal of Cancer,2021,148(10):2557-2570.
[10] Hart L L,Ferrarotto R,Andric Z G,et al.
Myelopreservation with trilaciclib in patients receiving topotecan for small cell lung cancer:results from a randomized,double-blind,placebo-controlled phase II study[J].
Advances in Therapy,2021,38(1):350-365.
Approval number: CN-107857 Expiration Date: 2023-3-26
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.
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