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Small cell lung cancer still mainly treated by Chemotherapy and Immunity 

Small cell lung cancer still mainly treated by Chemotherapy and Immunity .   Does small cell lung cancer have no driver gene mutations? 

In the two decades of vigorous development of targeted therapy, the field of small cell lung cancer is not completely without potential targeted drugs.

When it comes to targeted therapy for lung cancer, I believe everyone first thinks of classic non-small cell lung cancer targeted therapy drugs such as EGFR inhibitors and ALK inhibitors, but there are few targeted therapy options that can be used for small cell lung cancer.

In fact, small cell lung cancer has a certain degree of particularity among all lung cancers. In patients with this subtype of lung cancer, the driver gene mutation rate is completely different from other types of lung cancer. The common mutations such as EGFR in non-small cell lung cancer have a very low detection rate in small cell lung cancer, and the patients’ sensitivity to drugs is also Very low. However, driver gene mutations with a high detection rate in small cell lung cancer, such as EZH2, have no mature drugs that have entered clinical or preclinical trials.

Therefore, for patients with small cell lung cancer, chemotherapy is the “backbone” of systemic therapy, and emerging immunotherapy programs are the most promising “potential army”.

Targeted therapy: treatment of small cell lung cancer is repeatedly troubled

In fact, in the past two decades of vigorous development of targeted therapy, the field of small cell lung cancer is not completely without the emergence of potential targeted drugs.

For example, the δ-like protein-3 (DLL-3) antibody-conjugated drug ROVA-T (Rovalpituzumab tesirine) has shown a remission rate of up to 39% and a clinical benefit rate of 89% in phase I clinical trials. Unfortunately, in the subsequent phase II study, the remission rate of ROVA-T was only 16%, and the remission rate of third-line treatment was only 13%, which was far from reaching expectations.

The classic non-small cell lung cancer EGFR inhibitor gefitinib has failed clinical trials in the treatment of small cell lung cancer. Subsequent studies found that the mutation rate of EGFR in small cell lung cancer is only about 4%.

Imatinib has no obvious curative effect in the treatment of small cell lung cancer, whether it is a single agent or a combination of chemotherapy. Subsequent studies have found that the incidence of KIT mutations in small cell lung cancer is also very low, and abnormal activation of the PI3K/AKT/mTOR signaling pathway is prone to occur, which makes small cell lung cancer easily resistant to imatinib.

Anti-angiogenesis drugs are theoretically pan-cancer targeted drugs, and their target vascular endothelial growth factor (VEGF) expression rate in small cell lung cancer is also high. However, clinical research results show that common anti-angiogenesis inhibitors, including bevacizumab, sorafenib, etc., cannot prolong the survival of patients with small cell lung cancer.

Various experiences in the treatment of non-small cell lung cancer have “struck a wall” in front of small cell lung cancer.

However, the current curative effect of small cell lung cancer can never meet the needs of patients. Researchers can only “attack” this type of difficult-to-treat lung cancer again from two directions-one is to improve the effect of chemotherapy regimens, and the other is to discover another effective against small cell lung cancer. Treatment methods open up a new “battlefield.”

Chemotherapy: the “backbone” of systemic treatment of small cell lung cancer

Regardless of the NCCN guidelines in the United States or the CSCO guidelines in China, for patients with extensive-stage small cell lung cancer who cannot undergo surgery, the first choice is to include chemotherapy. As one of the most classic “troikas” of cancer treatment, chemotherapy occupies the “core” position in the systemic treatment of small cell lung cancer.

It is for this reason that research on chemotherapy for small cell lung cancer has never been interrupted. Researchers have been trying to develop an optimized plan to further improve the response rate and survival of patients with small cell lung cancer on the basis of existing chemotherapy regimens.

01 Rubycardine + Irinotecan: The remission rate is 62%!

According to the research results published at the latest World Conference on Lung Cancer (WCLC), the combined regimen of rubycatine + irinotecan for small cell lung cancer patients who have relapsed after receiving front-line treatment has achieved excellent results.

The results showed that in 21 patients with small cell lung cancer, the overall remission rate of the combination therapy was 62%, the clinical benefit rate was as high as 81%, and the disease control rate was 90%; the median duration of remission was more than 6.7 months, and the median remission rate was over 6.7 months. The progression survival time is more than 6.2 months.

The researchers pointed out that the patients included in the study included platinum-sensitive patients and non-sensitive patients, meaning that regardless of their sensitivity to platinum-based chemotherapy, they may benefit from this emerging dual-drug combination therapy.

02 Irinotecan liposomes: the remission rate is 44%!

Liposomes are a kind of high-efficiency and low-toxicity preparations with higher transfection rate and more significant curative effect. Irinotecan liposomes were approved in 2015 for the treatment of patients with advanced pancreatic cancer.

The results of a study also published on WCLC show that the use of irinotecan liposome injection to treat small cell lung cancer that has received platinum chemotherapy and has progressed disease can achieve ideal results.

Among the 25 patients, 1 patient achieved clinical complete remission, 10 patients achieved clinical partial remission, with an overall remission rate of 44%; in addition, 7 patients had stable disease, with a disease control rate of 72%. The median remission lasted for 2.99 months, the median progression-free survival was 3.98 months, and the median overall survival was 8.08 months.

03 Mitoenquinone Hydrochloride Liposomes: New drug clinical trials, recruiting!

Mitoenquinone is also a classic targeted drug that has been approved for marketing. It belongs to the same class of anthracyclines as doxorubicin (doxorubicin). The characteristic of this class of drugs is that they can treat more cancer types. Any other type of chemotherapeutic drugs should be abundant, and the curative effect is better. It is one of the most effective chemotherapy schemes. The types of cancers applicable to anthracyclines include leukemia, lymphoma, breast cancer, uterine cancer, ovarian cancer and lung cancer.

Clinical studies have shown that compared with doxorubicin, mitoxantrone has less cardiotoxicity and better safety. Its anti-tumor activity is equivalent to or slightly higher than that of doxorubicin, and is significantly higher than cyclophosphamide, fluorouracil, methotrexate, vincristine and cytarabine, and has a broad anti-tumor spectrum, which can be used for multiple cancer types the treatment. Mitoxantrone has a synergistic effect with many commonly used antitumor drugs, and only has partial cross-resistance with doxorubicin.

Immunotherapy: The most promising “potential army” in the treatment of small cell lung cancer

Compared with targeted drugs, immune drugs have shown potential worthy of attention in the treatment of small cell lung cancer.

At present, the “war” between several immune drugs and small cell lung cancer can be said to be in a tug of war. Nivolumab and pembrolizumab once showed good potential in the treatment of small cell lung cancer, but after a period of clinical application, they were withdrawn by pharmaceutical companies due to adverse reactions and other reasons. The most recent immunotherapy drug that has shown promising efficacy in the treatment of small cell lung cancer is atezolizumab.

01 Atezolizumab: overall survival time of 15.7 months

According to the latest published IMpower 133 trial results, the use of atezolizumab + carboplatin + etoposide for maintenance treatment of extensive-stage small cell lung cancer has achieved significant improvements in overall survival and progression-free survival.

The results of the study showed that patients with small cell lung cancer who received atezolizumab+carboplatin+etoposide maintenance treatment had a median overall survival of 15.7 months, which significantly exceeded 11.3 months in the carboplatin+etoposide treatment group; The median progression-free survival of patients treated with the combination regimen was 5.5 months, which also exceeded the 4.5 months of the control group.

02 Tilelizumab: excellent potential for the treatment of lung cancer, clinical trials are being recruited

Tilelizumab is a PD-1 inhibitor independently developed in some countries. The approved indications include lymphoma and urothelial carcinoma. At the ESMO conference in 2020, researchers once disclosed the efficacy of tislelizumab combined with chemotherapy in the treatment of patients with non-small cell lung cancer, which increased the overall remission rate of patients by more than half.

03 Teriplizumab: The indication for non-small cell lung cancer has been approved, marching towards small cell lung cancer!

Teriplizumab is also a domestically produced PD-1 inhibitor, and has been approved as an indication for the first-line treatment of non-small cell lung cancer. After obtaining this indication, the research side continued to advance towards the indication of small cell lung cancer, and the clinical trial of using the combination regimen of teriprizumab + chemotherapy to treat small cell lung cancer is ongoing.

Choose different treatment options for different lung cancers!

Small cell lung cancer and non-small cell lung cancer are both lung cancers, but their disease characteristics and treatment options can be said to be very different, and there are huge differences in treatment options.

In terms of targeted therapy alone, the number of targets recommended for detection in the current non-small cell lung cancer guidelines reaches 12, and the corresponding drugs or drugs under development for each target can significantly improve the survival of patients. However, the mutation rate of small cell lung cancer is very low. For example, the mutation rate of EGFR mutation in non-small cell lung cancer can reach 30%, and the mutation rate of small cell lung cancer is only about 4%.

The development of medical technology is a process of “getting knowledge from things”. With continuous in-depth exploration and analysis of the principles, we can find a more precise treatment plan. I believe that in the near future, researchers will be able to penetrate the “principles” of small cell lung cancer and find drugs that can really significantly prolong the survival of patients with small cell lung cancer.

On the way to fight cancer, human society has never stopped moving forward.

(source:internet, reference only)

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