Treatment options after advanced lung cancer was diagnosed

Treatment options after advanced lung cancer was diagnosed.  Diagnosis of cancer does not mean death. With appropriate treatment, you can also live with the tumor and create a better life of your own.

Not long ago, the latest global cancer report data was released. There were 2.26 million new cases of breast cancer worldwide, surpassing the 2.2 million cases of lung cancer, making it the world’s largest cancer.

But in recent years, as researchers have become more and more knowledgeable about lung cancer, weapons for treating lung cancer have emerged one after another, and lung cancer is no longer a terminal disease. Compared to the age when the level of medical care was lagging behind, you have many options for treatment, especially the emergence of molecular targeted therapy and immunotherapy, lung cancer has entered the era of precision treatment.

▌Traditional treatment methods: surgery, chemotherapy, and radiotherapy

For the vast majority of people who have not been exposed to cancer, the treatment of cancer still remains in the three traditional cognitions of surgery, chemotherapy and radiotherapy. Even today, we can still hear from many people the phrase “Is there any good way to not operate?” It is true that the three axes of traditional treatment are still the most widely used weapon in cancer treatment.

In the past two decades, some countries’s surgical treatment technology has developed by leaps and bounds. In most provincial or regional medical centers, minimally invasive methods such as VATS (Thoracoscopic Surgery) are widely used in routine cases. Some early cancer patients can be cured only by surgery. At the same time, most tumors can be staged correctly through surgery. Surgery means that the stage of the tumor is not very late, but in the clinic, only 20%-30% of patients are suitable for surgical treatment. Patients with stage III-IV small cell lung cancer have no significant improvement in survival after surgery, and surgery is not recommended.

Chemotherapy uses drugs to destroy cell proliferation. The faster the proliferation of cells, the easier it is to be killed by chemotherapy drugs. Because small cell lung cancer is more sensitive to chemotherapy drugs, the combined chemotherapy regimen of etoposide combined with cisplatin (EP) has been the first-line chemotherapy regimen in small cell lung cancer since the 1980s. Side effects such as nausea, vomiting, anemia and low platelets also make many patients miserable. Platinum-containing combined chemotherapy can prolong the survival of patients, but the prognosis of patients with advanced non-small cell lung cancer (NSCLC) is still extremely poor, with a 5-year survival rate of less than 15%.

Different from chemotherapy, radiotherapy uses radiation with different abilities to irradiate tumors to kill cancer cells and is a local treatment method. Radiotherapy is one of the better treatments for patients with advanced lung cancer who cannot choose surgery. Single radiation therapy can improve the median survival time of patients with stage III and IV non-small cell lung cancer in 10 months, but the 5-year survival rate is less than 5%. Because of its limited efficacy, it is often used in combination with other treatments in clinical practice.

According to good doctors, there are pros and cons for the treatment of lung cancer, but these treatments are far from enough for improving the quality of life of cancer patients and allowing them to live longer. It is precisely because of the active exploration of therapeutic weapons that more efficient treatment methods have emerged.

▌Targeted therapy: treat lung cancer like a target

The full name of targeted therapy is “molecular targeted drug therapy”. The “target” is some special molecules on tumor cells, and the treatment method is to use targeted therapy drugs to attack specific target molecules on tumor cells.

The discovery of epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer in 2004 brought us a highly sensitive and effective tyrosine kinase inhibitor (TKI) for EGFR mutations. In 2007, the emergence of the fusion gene of echinoderma microtubule-associated protein-4-anaplastic lymphoma kinase (EML4-ALK) has brought new and effective targets for the molecular development of lung cancer. At present, several lung cancer molecular targets and their targeted drugs are under study.

The EGFR mutation rate in non-small cell lung cancer is about 10% in North America and Western Europe, and 30%-50% in East Asia including China. Especially in Asian populations, the EGFR mutation rate is highest in women, non-smokers, and adenocarcinoma. 70%-80%.

Since the launch of the first generation of targeted drugs, targeted therapy has been refreshing the peak of the lung cancer treatment field. The EGFR-TKIs that have been marketed in some countries include the first generation of gefitinib, erlotinib and icotinib, the second generation of afatinib and dacomitinib, and the third generation of osimertin Ni, Ametinib.

In the past, multiple large-scale clinical studies have fully proved that the first-line and second-generation EGFR-TK inhibitors used in patients with EGFR-sensitive mutations can significantly improve the objective response rate (ORR) and quality of life compared with traditional chemotherapy, and significantly extend the patient’s life. Progression-free survival.

About 2/3 of the tumor tissues resistant to the first and second generation targeted drugs have T790M resistance mutations. The second-line treatment using the third-generation ERFR-TKI is significantly better than chemotherapy (effective rate: 71% vs 31%; PFS: 10.1 months vs 4.4 months), and the incidence of adverse reactions is lower.

In patients with non-small cell lung cancer, there are many gene mutations, and ALK mutations are called “diamond mutations” in the industry because targeted drugs are more sensitive to this target. Multiple evidences indicate that ALK mutation-positive patients take corresponding targeted The drug survival period is longer than that of EGFR mutation-positive patients. ALK gene rearrangement accounts for 4% to 7%. At present, the domestic approved ALK inhibitors include the first-generation crizotinib, the second-generation ceritinib and aletinib, and the third-generation TKI Laura, which is approved by the FDA and will be marketed in China in the future. Tinib.

For patients with ALK-positive advanced NSCLC, sequential treatment is an important treatment strategy. The results of a number of real-world studies have shown that through the “1+2” ​​sequential treatment model, the patient’s median OS can exceed 7 years, and the longest median OS can reach 89.6 months. In the future, patients can receive third-generation drug treatment after second-generation drug resistance appears. The survival time of ALK-positive patients will be further extended, and advanced lung cancer can also be managed as a “chronic disease”.

If targeted therapy is a landmark innovation in the field of cancer treatment, then immunotherapy is another blockbuster anti-cancer weapon. With the continuous deepening of clinical applications and research, people have found that targeted therapy is not a panacea. For some non-small cell lung cancer patients without driver gene mutations, their choices are limited, and there is still no breakthrough in the field of small cell lung cancer. In addition, the problem of drug resistance needs to be solved urgently. Where there is demand, there will be innovation, and immunotherapy emerges suddenly.

▌Immunotherapy: Let cancer patients live longer

Unlike chemotherapy and targeting, immunotherapy uses the body’s own immune system to fight tumors. To understand immunotherapy, one must first understand the relationship between tumors and the immune system.

Under normal circumstances, many mutations will inevitably accumulate during the occurrence and development of tumors, and these different mutations will encode many “different” antigens, so that the tumor cells that produce mutations are recognized and eliminated by the immune system. I have to lament that cancer cells are too cunning. In the process of fighting the immune system, mutated tumor cells can obtain a variety of ways to escape the surveillance of the immune system, which ultimately leads to the occurrence of tumors.

Aiming at the loss of immunogenicity of tumor cells, immunotherapy represented by PD-1/PD-L1 monoclonal antibody has entered the public’s attention. Immunosuppressants can inhibit the binding of PD-1 on the surface of T cells to PD-L1 ligand on the surface of tumor cells, reactivate T cells, and play a role in killing tumor cells.

In 2012, the PD-1 inhibitor Nivolumab (Nivolumab) was first reported to be successful in the second-line treatment of advanced NSCLC. Since then, NSCLC immunotherapy has ushered in a vigorous development.

Multiple PD-1/PD-L1 inhibitors are approved for the treatment of advanced NSCLC, including the PD-1 inhibitors nivolizumab, pembrolizumab, carrelizumab and tislelizumab; PD-L1 inhibitors atelizumab and duvalizumab.

Most PD-1/PD-L1 monoclonal antibodies are approved for second-line treatment of advanced NSCLC. Pembrolizumab is the first to be used for first-line treatment of advanced NSCLC. In 2020, ESMO released the 5-year follow-up of the KEYNOTE-024 study According to the data, the median survival period of pembrolizumab compared with chemotherapy group was 26.3 months and 13.4 months, and the 5-year survival rate was 31.9% and 16.3%, respectively. The driving gene-negative advanced NSCLC patients are away from the goal of “long survival”. One step closer.

While foreign immunotherapy is iteratively updated, the domestic immunotherapy field has also ushered in full development. On June 19, 2020, the PD-1 inhibitor carrelizumab was approved for lung cancer indications, combined with pemetrexed and carboplatin for the first-line treatment of advanced or metastatic non-squamous non-small cell lung cancer. The latest data show that the median overall survival period exceeded the 2-year mark, reaching 27.9 months; on January 13, 2021, tislelizumab was approved to combine paclitaxel and carboplatin for locally advanced or metastatic squamous non-small First-line treatment of cell lung cancer.

The indications of immunotherapy for non-small cell lung cancer have covered first-line and second-line; it can be used as a single agent or in combination; it is suitable for people to expand from non-squamous cell carcinoma to squamous cell carcinoma; not only for advanced patients, but also for locally advanced patients Bring clinical benefits.

The results of the PACIFIC trial showed that Durvalumab (Durvalumab) used in the adjuvant treatment of NSCLC with phase III concurrent chemoradiation prolonged progression-free survival (PFS).

Major breakthroughs in immunotherapy have also ushered in progress in the history of treatment for small cell lung cancer.

For more than 20 years, the treatment of small cell lung cancer (SCLC) has made little progress. The first-line standard treatment is still platinum (carboplatin or cisplatin) combined with etoposide. Although the effective rate is about 50%-70%, most patients are prone to For relapse and drug resistance, the median survival time is only 9 months to 11 months; only topotecan is approved for second-line treatment, and treatment methods are relatively scarce. Facing the unsatisfactory overall survival prognosis of SCLC patients, various studies have been launched to try to apply immunotherapy to break through the dilemma of SCLC treatment.

The IMpower133 study evaluated the efficacy and safety of atezolizumab combined with carboplatin/etoposide in the first-line treatment of extensive-stage small cell lung cancer. It is the first study to show a significant clinically significant improvement in OS compared with the current first-line standard regimen (OS: 12.3 months vs 10.3 months, HR=0.70). In addition, the median PFS and median duration of remission were prolonged and adverse reactions were controllable. Atelizumab combined with carboplatin/etoposide has become a new standard for the first-line treatment of extensive-stage small cell lung cancer.

With the deepening of the understanding of tumor immune mechanism, more and more immunological drugs have come out, and the clinical benefits have brought dawn to patients with lung cancer. What are the potentials of immunotherapy in the future? It is still worth exploring further.

▌Conclusion

From traditional treatment to the development of new anti-cancer technologies, cancer treatment methods have been continuously upgraded in the past 30 years, which has greatly improved the survival of lung cancer patients. Going back to the original question, the diagnosis of cancer does not mean that death comes. With appropriate treatment, you can also live with the tumor and create a better life of your own.

(source:internet, reference only)

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