As the largest malignant tumor with the highest incidence and mortality rate, the domestic lung cancer has more than 800,000 new medical records every year, and the five-year survival rate between China and the United States is only about 20%, which is huge room for improvement.

China is the largest country in cancer.

Among them, the most common cancers are lung cancer (17.9%) , colorectal cancer (12.2%), gastric cancer (10.5%), breast cancer (9.1%) and liver cancer (9.0%).

is the largest malignant tumor with the highest incidence and mortality rate. The new incidence of lung cancer in China exceeds .8 million every year. The five-year survival rate of in China and the United States is only about 0% , which has huge room for improvement.

Lung cancer is actually not something to be photographed.

If can be screened and diagnosed in the early stage of lung cancer and actively treated, the five-year survival rate can reach more than 90% . In addition, with the maturity of molecular targeted therapy and the arrival of the tumor immunotherapy era, significant progress has been made in the treatment of advanced lung cancer in recent years.

Only by facing fear and being clear about it can you "resist the enemy and win" and read the trend of medical treatment to explain the "promotion to fight monsters" to overcome lung cancer in detail.

Early screening: Low-dose spiral CT is the first choice

Many cancers have no symptoms in the early stage, and even if there are, they are very mild and are easily overlooked. Especially for lung cancer, most of the time is already in the advanced stage once diagnosed.

Lung nodules are the most common imaging manifestations of early lung cancer , and the final diagnosis depends on pathological diagnosis.

lung nodules are generally divided into three categories:

. Solid nodules: Some nodules less than 1cm, and more than 490% of the solid nodules are benign.

. Frosted glass nodules: The part with a CT value greater than -300 is invasive. If the range of this part exceeds 5mm, it may be invasive adenocarcinoma (LPA) in pure ground glass nodules. Surgical resection can be considered.

, partial solid, partial frosted glass: the possibility of malignancy is high.

study confirmed that if lung cancer is found in the early stage, its five-year survival rate can be close to 0%; "early early stage" lung cancer less than 1cm, the five-year survival rate can reach 2%.

However, according to statistics, the early diagnosis rate of lung cancer in China is only 19%, far lower than that of Japan's 38%. How to achieve early diagnosis and early screening? Actually very simple.

lung cancer screening usually has two ways: imaging examination, serological examination .

, and the only effective in early screening for lung cancer is (imaging examination) once a year for low-dose spiral CT of the lungs.

Imaging examination: Early lung nodules were found, CT is the first choice

Generally, the resolution of chest X-ray is limited, and it is difficult to detect early lung nodules, especially small nodules (diameter less than 1cm) . Therefore, the current consensus of domestic and foreign guidelines recommends that is the low-dose spiral CT in the lungs once a year as the preferred for early screening of lung cancer in , and its radiation volume is significantly reduced by 75% compared with conventional chest CT (only equivalent to taking a long-distance plane).

Global low-dose spiral CT manufacturers include: GE Medical, Philips , Siemens Medical, United Imaging Medical, Neusoft Medical, Encore Medical, Mingfeng Medical , Canon , Sanovia, Kanda, etc.

Among them, GE Medical, Siemens Medical, and Philips are the top 3 markets in the global and Chinese markets.

With the development of CT technology for nearly 50 years, it is transforming from the traditional scanning speed and row count (detector width) to the energy CT. Currently, energy CT mainly includes: double-layer detector spectroscopy CT, photon count CT, etc.

In terms of tumor imaging, energy CT can accurately identify super early tumor lesions .

For example, for lung nodules diagnosis, in addition to morphological size, density, volume and other parameters, energy CT can also obtain the iodine uptake rate and metabolism degree. provides more diagnostic information for the qualitative pulmonary nodules .In the field of

spectrum CT, Philips is one of the earliest players in the world to enter:

• In 2016, the world's first dual-layer detector spectrum CT; in 2021, the new generation of spectrum counting CT - Haoke Spectral CT was released globally.
• In May 2022, Haoke Spectral CT passed NMPA certification and was officially launched on the Chinese market .

Haoke Spectral CT

spectral CT Detect lung nodules

photon counting CT field, Siemens Medical CT NAEOTOM Alpha is the world's first photon counting CT.

• was licensed on the market in September 2021.
• In February 2022, it was approved to enter the "green channel" in China, and it is the first full-body CT to enter the "green channel" in China so far.

CT NAEOTOM Alpha

Photon CT Detection

In addition, the application of artificial intelligence in the clinical diagnosis of lung lesions has been implemented and is becoming more and more mature.

Three companies have been approved in China's clinical AI pulmonary nodule diagnostic system: Shenrui Medical, Tuixiang Technology, and Lianying Intelligent .

Serological examination (blood drawing test): The five major tumor markers can initially judge the risk of lung cancer

serum tumor mark detection has become one of the main means of lung cancer screening and diagnosis in recent years. Given the limitations of single tumor markers in terms of specificity and sensitivity, it is also advocated that multiple tumor markers be tested for .

Currently, there are five types of lung cancer-related tumor markers that have been clinically recognized by , namely: carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin fragment 19 (CYFRA 21-1), squamous cell carcinoma antigen (SCC), and gastrin release peptide precursor (ProGRP).

and tumor markers have also become a must-have item menu for various IVD companies.

Globally, Roche Diagnosis has become the top 1 in in vitro tumor diagnosis with the most comprehensive tumor detection project and accurate detection results, followed by Abbott , Siemens Medical , Beckman .

Chinese manufacturers: Mindray , New Industry, Antu, Mike , Changguang Huayi, Yahuilong are also catching up. At present, the testing projects can be compared with multinational companies, but there is still a gap in accuracy and precision.

If the serological lung cancer tumor marker is elevated, further needs to be excluded through lung imaging examination.

Pathological diagnosis: After qualitative "gold standard" of lung cancer

imaging examination, tissue biopsy or sections of lung lesions are usually required to determine the nature and pathological typing . This requires pathological diagnosis - the current gold standard for determining the classification and classification of lung tumors.

The main pathological types of Asian lung cancer patients: small cell lung cancer (SCLC) accounts for 10-15%; non-small cell lung cancer (NSCLC) accounts for 85-90%, mostly non-smoking people.

lung cancer can be divided into small cell lung cancer and non-small cell lung cancer .

• non-small cell lung cancer is divided into adenocarcinoma, squamous cell carcinoma , adenocarcinoma and large cell carcinoma; among them, adenocarcinoma dominates, followed by squamous cell carcinoma; 80% of the driver gene mutations that cause lung adenocarcinoma have been found, so molecular targeting drugs are very effective.
• small cell lung cancer is very different because of the different types of mutations. Currently, except for surgery and chemotherapy, no targeted drugs are available, and only immunotherapy can be cured.

Globally, the top three manufacturers with pathological diagnosis market share: Ventana (acquired by Roche Diagnostics), Dako (acquired by Agilent ), Leica (acquired by Danaher ) .

Other pathological diagnosis companies include: Thermo Fisher, Haulojie, Bidi, etc. In addition, in recent years, Chinese pathological diagnosis companies such as Dakowei, Anbiping, Maixin, and Aid Bio have gradually gained a foothold in the market.

Early lung cancer treatment: five years after minimally invasive surgery, if you are very lucky, you are still in the early stage of lung cancer, the treatment methods are not complicated.

Minimally invasive surgery for thoracic surgery can treat early lung cancer with little trauma and good efficacy. There are two methods: , one is single-hole thoracoscopy, and the other is surgical robot thoracoscopy .

single-hole thoracoscopy

surgical robot

patients do not need tracheal intubation during the operation, do not need catheter after the operation, and do not have a thoracic drainage tube; after the operation, you can even walk out of the operating room by yourself, and be discharged as soon as 24 hours, achieving the magical effect of treating early lung cancer and getting colds. 's five-year survival rate can reach 92%.

Things to note when minimally invasive surgery:

. Nodule size: If the nodule is particularly large and cannot be removed through a small wound, the wound needs to be longer;

. Nodule position: If it has a very close relationship with the blood vessels (such as close to the large blood vessels and the hilar), minimally invasive surgery is at certain risks;

. Thoracic adhesion: If the thoracic adhesion is particularly serious, it takes a long time to pass a thoracoscopy. In this case, you can choose to extend the wound.

Currently, thoracoscopy manufacturers in the Chinese market mainly include: Olympus (first), Fuji (second), Carl Stots (third), Pentax , German Wolf Card, Aohua Endoscopy , Kaili Medical, Mindray Medical , Yingmeida, etc.

surgical robot is the dominant player of da Vinci robot .

Non-early lung cancer treatment: surgery, radiotherapy, chemotherapy, interventional

For patients with non-early lung cancer, surgery, radiotherapy, chemotherapy, interventional treatment and drug treatment are still the main means (other non-main means also include traditional Chinese medicine treatment, etc.). Whether it is radiotherapy or drug treatment, precision and individualization have become the mainstream.

Surgery: Applicable to patients before stage IIIb

is suitable for patients with non-small cell lung cancer clinical stage I and II, and completely resectable stage IIIa; for some patients with stage IIIb and stage IV (isolated brain, adrenal and intrapulmonary metastasis), palliative surgery or surgery-based comprehensive treatment can also be performed.

Usually, after surgery, combined with comprehensive treatment such as drug treatment, radiation therapy, chemotherapy, etc.

Radiation therapy: suitable for patients with non-small cell carcinoma, precision is the trend

suitable for patients with non-small cell lung cancer who are not suitable for surgery or are unwilling to undergo surgical treatment.

Global radiation therapy manufacturers include: Varian, Medical Da , Yibiya, Ankerui, Boyilai, Yishite, Leitai Medical, Carl Zeiss , Xinrui Sunshine Particle Medical, United Film Medical, Boshi Medical, etc.

With the development of technologies such as AI, Internet of Things, big data, etc., radiotherapy has entered the era of smart precision . As the top 2 companies in the global radiotherapy field: Yikeda and Varian have all made arrangements in the field of precision radiotherapy.

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• Varian 's stereotactic radiation therapy (SBRT) technology has been included in the "Guidelines for Diagnosis and Treatment of Primary Lung Cancer (2022 Edition)".

Chemotherapy: Applicable to small cell carcinoma patients

for small cell lung cancer patients and non-small cell lung cancer patients who lose their chance of surgery ; chemotherapy is also valuable after the operation in addition to stage Ia patients.

chemotherapy drugs for lung cancer include paclitaxel , cisplatin, oxaliplatin, gemcitabine , vincristine , cyclophosphamide , etc., but they usually cause greater damage to the human body.

Interventional treatment: only as palliative therapy

mainly includes transvascular interventional chemotherapy and interventional embolization, radiofrequency ablation treatment, bronchial endoscopy treatment, radioparticle implantation treatment, etc.; it is a palliative local treatment and cannot replace surgery, radiotherapy and chemotherapy, etc.

mainly includes:

• Intravascular interventional treatment: directly vascular embolization or perfusion of chemotherapy drugs; including transcatheter arterial perfusion chemotherapy and transcatheter bronchial arterial embolization.
• Percutaneous lung puncture intervention treatment: is mainly used for peripheral lung cancer; including percutaneous lung puncture microwave ablation and radiofrequency ablation, argon and helium knife freezing, radioactive particle implantation, etc.

Lung cancer drug treatment: Targeted drugs, immunotherapy has become a trend

drugs are still the most important method for treating cancer.

In the lung cancer drug market, the global compound growth rate in the past five years was about 3%, and the compound growth rate in the next three years was about 11%.

Among them,

• Non-small cell lung cancer (NSCLC) market , there are many molecular targeted drugs and immunotherapy, and the competition among manufacturers is fierce;
• small cell lung cancer (SCLC) market , only two immunotherapy approved, and the market space is broad.

Gene detection : The first step in the treatment of non-small cell lung cancer

With the popularization of targeted drugs and immunotherapy, genetic testing (company diagnosis) is the first step in choosing targeted drugs and has also become a necessary option for patients with non-small cell lung cancer.

molecular targeting drugs and tumor immunotherapy drugs need to formulate different plans based on different races, pathology and gene mutation types of patients with lung cancer.

At present, no suitable driver gene has been found for small cell lung cancer, so gene detection is generally not required.

Through companion diagnosis, tumor patients can accurately judge whether the drug is effective for themselves based on lower-cost painless tests before taking the medicine, and avoid the pain of "trying the medicine with your body".



2022 latest third edition of "Non-small cell lung cancer NCCN Guidelines", recommends the 1 major targets that patients with non-small cell lung cancer should be tested as: EGFR (19del and L858R), EGFR (S768I, L861Q and/or G719X), EGFR 20ins, KRAS G12C, ALK, ROS1, BRAF, NTRK1/2/3, MET, RET, PD-L1.

Global gene testing manufacturers: Illumina is almost dominant, accounting for about 70% of the market; other manufacturers include Thermo Fisher Scientific, Roche Diagnostics, etc.



Chinese gene detection manufacturers: BGI , Aid Bio, and Pan-Gene are also good choices.

molecular targeting drugs: the second step of treatment of non-small cell lung cancer

According to the different genotyping detected, patients with non-small cell carcinoma can choose different molecular targeting drugs.

At present, molecular targeted drugs are only effective for non-small cell lung cancer. Most drugs have been iterated to the second, third and fourth generations; the products under development of various companies are also mainly concentrated in the third and fourth generation targeted drugs .

data shows that after the birth of the targeted drug , in patients with advanced non-small cell lung cancer achieved tumor shrinkage.

molecular targeting drug is a treatment method for the already clear oncogenic sites (protein molecules, gene fragments) at the cell molecule level. Because it acts accurately on the lesions and will not affect normal tissue cells, it is also called a "biomissile". But there is currently no drug that is very effective for small cell lung cancer.

first-generation targeted drugs do not bind very strongly to targets;

second-generation targeted drugs irreversibly bind to targets, and the targets are wider;

third and fourth generation targeted drugs overcome the drug resistance problems of the first and second generations and penetrate the blood-brain barrier more effectively.

Asian lung cancer patient population, EGFR mutations and ALK mutations account for the highest proportion, exceeding 55%; other mutation types include ROSI mutations, BRAF mutations, MET mutations and other .



Genotyping for Asian lung cancer patients



EGFR mutation:

third-generation targeted drugs are the mainstream, AstraZeneca (Teresa) has the best sales

EGFR mutation is the largest mutation type in non-small cell lung cancer, accounting for 0% . It is also the area with the most market layout of lung cancer targeted drugs. The drugs have been iterated to the fourth generation (on the market in 2021); the market is still dominated by third-generation targeted drugs .

• In 2002, the world's first EGFR mutant targeted drug, AstraZeneca's gefitinib (Iresa), was launched in Japan, opening the era of precision medicine for lung cancer.

EGFR targeted drugs: 7 drugs have been approved worldwide, and 8 drugs have been approved in China (all included in medical insurance).





The third generation targeted drugs that have been approved for marketing in China include:

• AstraZeneca (Teresa), approved in 2017; htmlm l14
• Housen Pharmaceutical (Amero), approved in 2020;
• Alice Pharmaceutical (Eversha), approved in 2021;

all have been included in the medical insurance .

AstraZeneca's osimertinib (teresar) is the first third-generation EGFR TKI to be launched. has been approved for the first-line treatment of advanced non-small cell lung cancer (NSCLC) with EGFR mutation in China in 2019, has maintained the highest sales of lung cancer drug for Chinese hospitals . Teresa is also AstraZeneca's highest revenue product. It exceeded the US$5 billion revenue threshold for the first time in 2021, ranking seventh among the world's best-selling tumor drugs.

study showed that the objective response rate (ORR) of osimertinib in patients with T790M mutation after first and second generation EGFR TKI treatment was 62%-71%, with a median progression-free survival (PFS) of 9.7-12.3 months, and a median overall survival (OS) of 23.2-26.8 months. The efficacy and safety are far better than traditional chemotherapy.

Other third-generation targeted drugs also include two self-developed products from Chinese manufacturers: Hausen Pharmaceutical (Ametinib), Alis Pharmaceutical (Vometinib) .

ametinib is China's first independently developed three-representative tyrosine kinase inhibitor (TKI); data show that patients with ametinib as the first-line treatment have significantly extended progression-free survival (PFS) and sustained remission time (DoR)—mPFS 19.3 months vs 9.9 months (HR 0.46, P 0.0001), mDoR 18.1 months vs 8.3 months (HR 0.38, P0.0001); At present, its other two EGFR inhibitors, HS-10376 (third generation) and HS-10375 (fourth generation), have entered the clinical stage.

VometinibThe data released on the latest ESMO shows that the 10 patients treated first-line have different degrees of tumor target lesions, with a median tumor shrinkage of -51.8%, and a disease control rate (DCR) of 100%. Among them, the tumors in 6 patients met the objective remission criteria, and the confirmed ORR was 60%.

No fourth generation targeted drugs have been approved in China.

Takeda Pharmaceutical took the lead in occupying the fourth generation of targeted drug market, and mobotinib also showed better efficacy. The

study showed that the total response rate (ORR) evaluated by the independent review committee (IRC) was 40%, and the duration of remission (DOR) was 13.0 months; while the total response rate in patients who had previously received first-generation, second-generation or third-generation EGFR TKIs was less than 10%, and the median progression-free survival was less than 4 months.

EGFR target market competition is fierce, the pattern is relatively mature, and it has entered the red ocean; new manufacturers may only break through from rare mutations, combined drugs, prices, etc.



ALK mutation:

second-generation targeted drugs are the mainstream, Roche (aletinib) has the best sales

ALK mutation is the second largest gene mutation type in Asian lung cancer patients, accounting for about % . At present, the third-generation drug has been launched, but the second-generation targeted drug is still the main one.

Compared with other gene mutations, patients with ALK gene mutations can use corresponding targeted drugs to inhibit tumors very effectively and obtain a longer survival period, so it is also called "diamond mutation".

ALK positive is the type of non-small cell lung cancer that is more prone to brain metastasis in . Up to 30% of patients with ALK+NSCLC have brain metastasis when they are diagnosed, and 55% of patients will have brain progress within two years of ALK+NSCLC diagnosis. Therefore, improving drug resistance and breaking through the blood-brain barrier of is an important advantage of the new second and third generation ALK inhibitors .

ALK targeted drugs: 5 drugs have been approved worldwide, and 6 drugs have been approved in China (4 are included in medical insurance).





China's ALK inhibitor market size has grown by as much as 65.5% in the past five years. It has now been launched in all second-generation and third-generation targeted drugs in the world.

The second-generation targeted drugs that have been approved for marketing in China include:

• Roche (aletinib), approved in 2018 and have been admitted to medical insurance;
• Novartis (seretinib) ), approved in 2018 and has been admitted to medical insurance;
• Betat Pharmaceutical (ensatinib), approved in 2020 and has been admitted to medical insurance;
• Takeda Pharmaceutical (bugatinib), approved in August 2022 and has not yet entered medical insurance.

The third generation targeted drugs that have been approved for marketing in China include:

• pfizer (loratinib), which was approved in 2022 and has not yet been admitted to medical insurance.

From a technical perspective:

• Roche (aletinib), Novartis (seritinib), Takeda (bugtinib), Beda (ensatinib) is a second-generation ALK TKI to solve the drug resistance problem caused by crizotinib 's difficulty passing through the blood-brain barrier, mutations such as L1196M, G1269A, and ALK amplification;
• Pfizer (laratinib) is a third-generation ALK TKI to solve the drug resistance problem caused by the G1202R mutation of the second-generation ALK TKA.

From the perspective of sales in 2021:

• Roche (aletinib) ranked first in the sales of sample hospitals in China with 550 million yuan, and also ranked first in the ALK inhibitors with sales of US$1.49 billion in the world;
• Novartis (seritinib) sold in sample hospitals in China with 66 million yuan, and has not seen a large volume due to its late launch.



other mutations:

Blockstone Pharmaceuticals (Phukethua), Hutchison Pharmaceuticals (Worresha) have been included in medical insurance

Other rare target mutations include:

• ROS1 mutation (about 2%): Most of them are young, non-smoking lung cancer patients, most of which are lung adenocarcinoma.
• BRAF mutation (about 2%): 50% of them are BRAF V600E site mutations, which are more likely to occur in adenocarcinoma, women, and non-smoking patients.
• MET mutation: the incidence rate in lung adenocarcinoma is 3%.
• RET mutation (about 1%).
• KRAS mutation: mainly in lung adenocarcinoma.

Other targeted drugs: 7 approved globally, 3 approved in China (2 included in medical insurance).



The rare mutation target of lung cancer is still the blue ocean.

drugs that have been approved for marketing in the Chinese market include:

• and Huang Pharmaceutical (Worisa), targeted MET, approved in 2021, and have been included in medical insurance;
• Blockstone Pharmaceutical (Phukethua), targeted RET, approved in 2021, and have been included in medical insurance;
• html l3 Roche (Entritinib), targeting ROS1/NTRK/ALK, was approved in 2022, but has not been admitted to medical insurance;

cornerstone pharmaceutical , which was approved in 2021, is a first-class precision targeting drug and is also the first approved selective RET inhibitor in China. It is used for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) patients who have received platinum-containing chemotherapy-containing transfection rearrangement (RET) gene fusion positive.

has been approved worldwide drug manufacturers including:

Novartis (2 models: targeted BRAF, targeted MET), which is not available in China;

• Novartis targeted BRAF (darafinib + trimetinib) global sales in 2021 were US$1.693 billion Yuan (including lung cancer, melanoma, thyroid cancer);

Roche (targeted ROS1), approved in China in 2022 but not yet included in medical insurance;

Merck (targeted MET), Eli Lilly (targeted RET), and Amgen (targeted KRAS) were not approved in China.

Immunotherapy: The future of cancer treatment

is different from the mechanism of action of traditional treatments. immunotherapy achieves anti-tumor effects by reactivates the immune response of human T cells to the tumor. Its efficacy is more lasting and is suitable for all lung cancer patients, including small cell lung cancer and non-small cell lung cancer.

Tumor immunotherapy can be divided into five categories according to different mechanisms of action:

Targeting T cell immunomodulators (PD-(L)1, CTLA4 monoclonal antibody, etc.);

Other immunomodulators (TLR, interferon-α/β receptor 1 (IFNAR1) agonist, etc.);

Tumor vaccine (such as HPV vaccine , mRNA tumor vaccine);

Tumor vaccine (such as HPV vaccine , mRNA tumor vaccine);

Tumor vaccine (such as HPV vaccine , mRNA tumor vaccine); 4

cell gene therapy (CAR-T, oncolytic virus , etc.);

multispecific drugs



mAb field:

K medicine, O medicine, T medicine, I medicine Top four

In September 2014, Bristol-Myers Squibb PD-1(L)1 monoclonal antibody Opdivo was approved in Japan for the treatment of unresectable melanoma, and opened the era of tumor immunotherapy .

PD-1(L)1 is a "targeted T cell immunomodulator". So far, immunotherapeutic drugs on the market are still mainly concentrated in "targeted T cell immunomodulator".

Different targets have different effects on different cancer types , for example, lung cancer has the best effect on PD-(L)1 target . Therefore, lung cancer is also the largest market segment in PD-(L)1, accounting for as much as 5%.



Global PD-(L)1 inhibitors have sales in various tumor fields, among which lung cancer has the largest area and the highest sales, far ahead of other cancer

In the past three years, as PD-(L)1 checkpoint inhibitors have become the standard treatment method for patients with advanced non-small cell lung cancer, the use of old non-targeted chemotherapy drugs has decreased significantly, and the median survival of first-line treatment for patients with advanced lung cancer has been extended by nearly half a year. Judging from the approved drugs for

, the current lung cancer immunotherapy drugs that have been launched in China are basically synchronized with the global level.

PD-(L)1 monoclonal antibody (lung cancer): 5 models have been approved worldwide, and 8 models have been approved in China (3 models have been included in medical insurance).



Drugs approved for marketing in the Chinese market: covers 8 approved lung cancer indication PD-(L)1 monoclonal antibody,

• 4 foreign investment: BMS O-Pharma (approved in 2018), Merck KPharma (approved in 2019), AstraZeneca IPharma (approved in 2019), Roche T-Pharma (approved in 2022) , none of which have been approved for medical insurance;
• self-developed 4 models in China: Hengrui Medicine Erica (approved in 2020) , Innovent Biologics Daboshu (approved in 2021) , BeiGene Bai Ze'an (approved in 2021), the above three have been included in medical insurance; cornerstone pharmaceutical company Zejiemei (approved at the end of 2021) will participate in the 2022 medical insurance negotiations.

In 2021, was approved for lung cancer indication and included in medical insurance , and ranked among the top three in sales in China PD-(L)1, which is highly inclined.

• Hengrui Medicine Erica sales of 4.89 billion;
• Innovent Biologics Daboshu sales of 3 billion;
• BeiGene Baizean sales reached 1.621 billion;

Merck K medicine and Bristol-Myers Squibb O medicine are still the first echelon in the world.

KEYTRUDA (K drug) is the PD-(L)1 monoclonal antibody with the most approved indications and the highest sales volume in the world; it is also the immune checkpoint inhibitor , which has the most comprehensive indications for lung cancer.

• As of the end of 2021, 29 indications have been approved for the treatment of 318 tumors including melanoma, lung cancer, head and neck squamous cell carcinoma, Hodgkin's lymphoma, urothelial cancer, MSI-H or dMMR solid tumors, gastric cancer, colorectal cancer, breast cancer, cervical cancer, B-cell lymphoma, liver cancer, Merkel's cell carcinoma and other .

OPDIVO (O drug) is the world's first PD-(L)1 monoclonal antibody approved by , and is also an immune checkpoint inhibitor , which is the early, middle and late stages of lung cancer in .

• In March 2022, the US FDA approved OPDIVO combined with chemotherapy for neoadjuvant therapy in specific resectable non-small cell lung cancer; it is the first and only approved preoperative (early) immunotherapy for NSCLC.

In addition, Opdivo+Yervoy is the first and only tumor immunotherapy drug combination approved by the FDA, targeting two different immune checkpoints, PD-1 and CTLA4, respectively. Compared with chemotherapy, the risk of death is reduced by 21%, the annual survival rate is 63%, the two-year survival rate is 40%, and the three-year survival rate is 33%.

Opdivo helps T cells discover and kill tumor cells. Yervoy stimulates T cell activation and proliferation, and some T cells stimulated by Yervoy can be converted into memory T cells, maintaining the immune response for a longer time.

Roche (T drug) , AstraZeneca (I drug) In addition to non-small cell carcinoma, is the only small cell lung cancer treatment drug in the world .



small cell immunotherapy drug

small cell lung cancer (accounting for 10% of Asian patients) is the most difficult area for lung cancer to overcome. There was almost no medicine before to cure .

• In March 2019, the FDA approved Roche (T drug) combined with chemotherapy for the first-line treatment of extensive-stage small cell lung cancer; it became the first immunotherapy for to treat small cell lung cancer in ; was approved in China in 2020 ;
• In March 2020, the FDA approved AstraZeneca (I drug) combined with chemotherapy for the first-line treatment of extensive-stage small cell lung cancer; was approved in China in 2021 .

Compared with chemotherapy, these two immunotherapies extended the patient's overall survival (median OS: 12.3 months vs 10.3 months), reducing the risk of disease progression or death by 23% (median PFS: 5.2 months vs 4.3 months).

In the field of small cell lung cancer, domestic innovative drugs are also constantly making breakthroughs.

• In June 2022, Fuhong Hanlin gave an oral report on its PD-1 monoclonal (Slulizumab) international multicenter phase III clinical study (ASTRUM-005) for first-line extensive-stage small cell lung cancer (ES-SCLC) at the annual meeting of the American Society of Clinical Oncology (ASCO). In the future, it may become the first self-developed small cell lung cancer immunotherapy in China.

PD-(L)1 dual antibody, new immune checkpoint inhibitors, etc., will further play a role in the fields of immune resistance, small cell lung cancer, etc. Immunotherapy represented by PD-(L)1 has gradually become the basic therapy for advanced lung cancer, and is also advancing to neoadjuvant and postoperative adjuvant treatment.



Future fields:

Multispecific drugs, cell gene therapy, tumor vaccine is the trend

As more and more monoclonal antibody targets enter the Red Sea, it is becoming more and more difficult to achieve a breakthrough in disease treatment with a certain target; and a major defect of monoclonal antibody immunotherapy is that it is only effective for a small number of patients, such as PD-1/PD-L1 monoclonal antibody is only effective for less than 20% of patients.

Therefore, the future of immunotherapy cannot be only in monoclonal antibodies.

multispecific drugs: Only two lung cancer drugs have been approved in the world, and it is not available in China.

has usually added another effect on the design of classic drugs, forming multiple drug-target interfaces, thus breaking through the limitations of single targets horizontally.



Multispecific immunotherapy lung cancer drug

Currently, for lung cancer treatment, there are only two multispecific drugs for globally on the market :

• dual anti-drug html developed by Janssen 4Rybrevant, which acts on EGFR and MET targets, is also the first lung cancer treatment drug for inserting mutations in EGFR exon 20;
• (ADC) antibody-conjugated drug developed by Sankyo/AstraZeneca Enhertu.

cell gene therapy: It is still in the exploration stage, no lung cancer drugs have been approved in the world

cell and gene therapy includes: CAR-T, mRNA drugs, etc. More than 20 related products have been approved for marketing around the world, but there are no indications for lung cancer.

CAR-TAs a more mature field of cell gene therapy, has made blood tumors no longer a terminal illness and a chronic disease that can be cured or controlled for a long time .



In the past two years, the indications of somatic tumors of CAR-T therapy have become the key breakthrough direction of major enterprises. Currently, solid tumor targets mainly include GPC3, Claudin 18.2, MSLN, etc.

• As of April 2022, clinical trials of cell gene therapy for solid tumors accounted for 43%, an increase of 44% year-on-year.

MedTrend medical trends, like 244

It is gratifying that at the just-held Global Lung Cancer Conference, Professor Dong Xiaorong of Union Hospital of Huazhong University of Science and Technology reported the preliminary results of aPD1-MSLN-CART phase I clinical trial of metastatic lung cancer, and showed safety and effectiveness. This also provides another strong evidence for CAR-T therapy in the treatment of solid tumors. 1 case of partial remission (PR) after treatment, 2 cases of stable disease (SD), and 1 case of disease progression; none of the patients had cytokine release syndrome or neurological symptoms, and there was no dose-limiting toxicity.

Tumor vaccine: lung cancer indications are all in the preclinical stage

The newly emerging mRNA vaccine giants Moderna and BioNTech are all planning tumor vaccines.

• In February 2022, Moderna announced its vaccine mRNA-4359 for cancer. The first considerations for its adaptation are advanced or metastatic skin melanoma and non-small cell lung cancer (NSCLC); in addition, Moderna is developing an mRNA vaccine mRNA-4157. By using it in combination with K drugs, it can trigger the immune system, make it more sensitive to PD-1 inhibitors, and reduce the risk of cancer recurrence.
• In August 2022, BioNTech combined with researchers from Harvard Medical School, Washington University in St. Louis and other institutions to publish a research paper in the journal Cancer Cell; the study reported a phase 1b clinical trial that uses the individualized neoantigen cancer vaccine NEO-PV-01 combined with chemotherapy and the anti-PD-1 drug pembrolizumab for the first-line treatment of metastatic non-squamous non-small cell lung cancer, proving that this treatment regimen is well tolerated and induces neoantigen-specific CD4+ T cell response with an effector phenotype.

As of the first half of 2022, about 30 lung cancer targeted drugs and immunologic drugs have been approved worldwide, and has been listed in China for about 20 models.

The future treatment direction of lung cancer is mainly sequential targeted treatment of , pan-cancer species (same treatment for different cancers), , and individualized treatment (same cancer treatment for different cancers) .

• sequentially, refers to the alternating use of multiple drug regimens; sequentially targeted therapy, refers to the longitudinal direction including surgery, chemoradiation, targeted therapy, and immunotherapy; the horizontal direction includes the alternating first and second-line drugs. makes patients with no chance of surgery transform into resectable treatments .
• heterocancer treatment, is one of the most promising emerging targeted drug research and development directions, especially in targets such as NTRK and RET, the market for pan-cancer specific targeted drug is expected to achieve rapid development.
• the same cancer treatment, means that the diagnosis and treatment plan is tailored for individuals through concomitant diagnosis according to the gene sequencing of different individuals.

Through early diagnosis and early screening and scientific prevention and treatment, cancer is no longer a "terminal illness" in the traditional sense. There are also multiple cancers that can be cured. We believe that someday in the future, lung cancer will become a chronic disease.

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