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What are the current treatments for Advanced Lung Cancer?
What are the current treatments for Advanced Lung Cancer? Advanced lung cancer = terminal illness? No, there are a few more options to treat it.
Ten years ago, advanced lung cancer might be incurable. But today, advanced lung cancer is not a terminal disease. Combination Immunotherapy is the future direction of curing cancer, which has already been a consensus in the industry.
However, the next question is, under the current circumstances, what is the immune combination? How to perform the immune combination? The doorway is quite complicated.
▌To cure advanced lung cancer, we must rely on a combined immune program
Is lung cancer incurable? Obviously not.
For early lung cancer, surgery or stereotactic radiotherapy still has a certain “radical”, but for patients with advanced lung cancer, because the tumor has metastasized, “cure” has become an almost impossible task.
Targeted therapies have been high hopes. However, on the one hand, not everyone has the opportunity to use targeted therapy; on the other hand, targeted drug resistance has become a hurdle that targeted therapy is difficult to overcome.
Previous cognitive models believe that mutations are the cause of cancer. The new theory believes that cancer is the product of changes in the tissue ecosystem. In fact, the human body is constantly producing cancer cells, but they will not develop into cancer because cancer cells are restricted by the body’s various systems, especially the immune system.
The reason that targeted drugs cannot cure cancer is that although targeted drugs can inhibit cancer cells, they cannot “ecology” of the human body. As long as cancer cells are still in a dominant position, they can quickly “adapt” to targeted drugs and produce “evolution”. “.
It was not until the emergence of immune checkpoint inhibitors that it was truly possible to cure advanced lung cancer. Immune checkpoint inhibitors represented by PD-1/PD-L1/CTLA-4 monoclonal antibody do not kill and inhibit cancer cells, but restore the function of human immune cells and restore the balance of the human body’s “ecological environment”. When cancer cells are no longer in a dominant position, the cancer is cured.
Although immunotherapy is only a few years old, existing research data shows that about 15% of patients with advanced lung cancer can live for 5 years after receiving immunotherapy, and some patients have even achieved clinical cure. In the field of melanoma, where immune checkpoint inhibitors were used earlier, “super survivors” who have survived for more than 10 years have been produced.
You know, this is only the data of immune single-drug therapy. At present, the long-term survival data of the combined immunization program has yet to be announced, which is expected to improve the problem of low efficiency of immunotherapy. The hope of curing cancer seems to have fallen to the combined immunization program.
▌What are the combined immunotherapies?
Immunotherapy and other anti-cancer methods have produced surprising synergistic effects. At present, the more commonly used Combination Immunotherapy programs include: immune combined chemotherapy, immune combined anti-angiogenesis therapy, immune + chemotherapy + anti-angiogenic therapy four-drug regimen, dual immune combination, immune combined radiotherapy, etc.
1. Immune combined chemotherapy
The effective rate of immune single drug is low, and researchers have found that effective people tend to have higher PD-L1 expression (but not absolute, some PD-L1-negative patients are still effective when receiving immunotherapy). Therefore, immune single drug The indications are limited to people with high PD-L1 expression.
Until later, the immune combination chemotherapy regimen broke the restriction of PD-L1 expression. Whether it is PD-L1 negative, positive, or high expression, all can accept the immune combination chemotherapy regimen. Immunization combined chemotherapy regimen has also become the most commonly used immune combined regimen.
However, do you know that chemotherapy becomes the partner of immunotherapy, but it is not so taken for granted. Chemotherapy has the characteristics of “killing one thousand enemies and self-inflicting eight hundred”. At the beginning, researchers believed that chemotherapy would directly or indirectly damage killer tumor T cells, and release a large amount of antigens to cause immunosuppression, etc., and immunotherapy “Clash”.
However, the clinical trial data is different. The combination of chemotherapy and immunotherapy has not affected the efficacy of immunotherapy, but has increased. Studies have found that chemotherapy can not only kill tumors directly, but also participate in the positive regulation of the immune system and change the local immune microenvironment of tumors, such as: activating dendritic cells and increasing antigen cross-presentation; recruiting T cells into tumors; reducing immunity Suppressor cells and regulatory T cells; etc.
In 2020, the journal Cancer published a meta-analysis that included 5931 patients from 10 studies. The results found that the incidence of immune-related adverse reactions above grade 3 is low when PD-1/PD-L1 monoclonal antibody is combined with chemotherapy In a single drug. In people’s common sense, the adverse effects of the combined regimen should be greater, but combined chemotherapy not only enhances the efficacy of immunotherapy, but also reduces immune toxicity.
2. Immune combined anti-angiogenesis therapy
The adverse reaction of carrelizumab “capillary hyperplasia”, the incidence rate is nearly 80%. Therefore, when doctors recommend the use of carrelizumab, they will also recommend a combination of an anti-angiogenic drug: apatinib. Combining anti-angiogenic drugs can reduce the incidence of “capillary hyperplasia” with carrelizumab to about 15%.
It is undeniable that the combination of anti-angiogenic drugs does have the purpose of alleviating adverse reactions. However, judging from the whole incident, immune combined anti-angiogenic therapy is also a highly potential immunotherapy combination plan, and it is by no means purely to reduce specific adverse reactions. simple.
Tumor growth maintains the immunosuppressive microenvironment required for its growth and invasion by manipulating the vascular system, immune system, and promoting chronic inflammation. Both anti-angiogenesis and immunotherapy act on the tumor microenvironment, and more and more research evidence shows that the two can affect each other’s functions and have potential synergistic anti-tumor effects.
At present, no immune combined anti-angiogenesis treatment plan has been approved, and many ongoing clinical studies of immune combined anti-angiogenesis therapy are mostly phase I/II, but this does not affect the real-world immune combined anti-angiogenesis treatment plan. usage of.
3. Four-drug regimen of immune + chemotherapy + anti-angiogenesis treatment
Experts use the immune + anti-vascular combination scheme without approval. Part of the confidence comes from the IMpower150 study of atilizumab, which explores the comparison of atilizumab + dual-agent chemotherapy + anti-angiogenesis The efficacy and safety of dual-drug chemotherapy + anti-angiogenesis therapy.
The results showed that the progression-free period of the four-drug regimen group was extended by 1.5 months compared with the three-drug regimen group, and the median overall survival was extended by 4.9 months to 19.8 months.
In addition, the study also included some patients with positive EGFR/ALK gene mutations, and the overall survival of the four-drug regimen was also significantly improved. At present, for patients with late-line resistance to EGFR and extensive progression, the recommended treatment plan in the CSCO guidelines is chemotherapy + anti-angiogenesis therapy. The regimen of immunization + chemotherapy + anti-angiogenesis therapy can provide a better choice for the follow-up treatment of patients with advanced non-small cell lung cancer with EGFR/ALK mutations.
4. Double immunization plan
The dual-immune combination regimen can be said to be a hot spot in the field of lung cancer. In May 2020, the nivolumab + ipilimumab ± two-cycle chemotherapy combination regimen was officially approved by the FDA. Ipilimumab (CTLA-4 inhibitor) and Nivolumab (PD-1 inhibitor) are both immune checkpoint inhibitors, and they have unique complementary effects:
The role of CTLA-4 pathway mainly occurs in lymph nodes, while the role of PD-1 pathway not only occurs in lymph nodes, but also in peripheral tissues and tumor tissues.
CTLA-4 antibody mainly acts on the early stage of T cell development, increasing activated T cells from the source and enhancing anti-cancer ability. The PD-1 antibody mainly acts in the late stage after the maturation of T cells, releasing the anti-cancer ability suppressed by the tumor.
Previously, the use of ipilimumab was often due to too many side effects that many patients could not tolerate. The side effects can be reduced by reducing the dose, but it will lead to insufficient curative effect and treatment failure, which greatly limits its use. Through the combination with nivolumab, the researchers found that reducing the dose of ipilimumab in the combination regimen did not lead to a decrease in efficacy and greatly reduced side effects.
In addition, both ipilimumab and nivolumab can stimulate the production of memory T cells, and memory T cells are the key to long-term benefits and long-term survival of immunotherapy. People are also optimistic about the long-term benefits of the dual immunization program and look forward to the release of follow-up data.
Other immunization combinations
In addition to the above-mentioned immune combination program, there are also immune combination radiotherapy, and even immune combination targeted therapy.
Similar to chemotherapy, the combination of radiotherapy and immunotherapy can also play a synergistic effect, and it has begun to show signs. Positive EGFR/ALK gene mutations used to be the “forbidden zone” of immunotherapy. Not only did it fail to achieve good results, it would increase the risk of serious adverse reactions. However, the research on immune combined targeting is not “annihilated.” This combination is still very likely to bring hope of cure for lung cancer.
Not only that, new types of immune checkpoint inhibitors, such as TIM-3, LAG-3, TIGIT, and so on, are about to emerge. In addition, other immunotherapies such as tumor vaccines and TIL therapies are seeking breakthroughs and are expected to join the strategy of immune combination.
The future must be bright.
(source:internet, reference only)