Whether it is the number of patients or deaths, lung cancer has always been in the position of "boss", and small cell lung cancer is extremely difficult to deal with in all types of lung cancer. Strictly speaking, small cell lung cancer can not be regarded as a lung disease, but should be a systemic disease, in the traditional treatment model, small cell lung cancer treatment mainly relies on chemotherapy and radiation therapy, with the development of immunotherapy, small cell lung cancer treatment mode has undergone some changes.
Today we will summarize all the treatments for small cell lung cancer.
1. Chemotherapy drugs
With the publication of the 2022 CSCO guidelines, there are not many highlights and updates on chemotherapy drugs and protocols for small cell lung cancer. Chemotherapy regimens usually use irinotecan or etoposide plus platinum (cisplatin, carboplatin, loplatin). Second-line options can be selected for topotecan, paclitaxel, docetaxel, gemcitabine, vinorelbine, temozolomide, and other chemotherapy.
Due to the high myeloid toxicity of the chemotherapy drug for small cell lung cancer, this year's CSCO guidelines have added a recommendation for the chemotherapy protective drug terracililide. Terracillyl is a short-acting CDK 4/6 inhibitor used to reduce the incidence of bone marrow suppression in patients with extensive-stage small cell lung cancer who receive certain types of chemotherapy.
Small cell lung cancer has a high sensitivity to chemotherapy and has a good recent treatment effect, but due to the short time of cancer cell multiplication, the remission period is often relatively short, and many patients develop after a few months of maintenance. Therefore, for patients with positive lymph nodes after radical surgery, postoperative adjuvant radiotherapy is required. In patients with limited time who are not operating, guidelines recommend simultaneous or sequential radiotherapy.
2. Immune drugs
Although there are more than a dozen varieties of PD1/PDL1 immune checkpoint inhibitors, there are relatively limited immune drugs recommended by the real guidelines and approved by the state for small cell lung cancer. For example, O drug, in August 2018, the FDA approved the O drug navulijultumab third-line treatment of small cell lung cancer, but the two major phase III clinical trials of validation failed, so in December 2020, the indications for small cell lung cancer of O drug were withdrawn. The same is true of K-drugs, keynote-604 Phase III clinical studies show that pambolizumab combined with chemotherapy first-line treatment of small cell lung cancer can reduce the risk of disease progression (4.5 months vs 4.3 months), but OS did not differ significantly, for this reason, on March 1, 2021, Merck actively withdrew pambolizumab as an indication for broad-stage small cell lung cancer.
The immune drugs recommended by the guidelines for small cell lung cancer are all imported PD-L1 inhibitors, one is dovalizumab and the other is atenibizumab. In March 2019, the FDA approved atenizumab (Taishengqi, T drug) combined with the chemotherapy drugs carboplatin and etoposide for the first-line treatment of widespread small cell lung cancer, which is the first immunotherapy drug approved for the first-line treatment of small cell lung cancer. In the IMpower133 study, atezizumab plus carboplatin + etoposide extended median OS (12.3 vs 10.3 months) and median PFS (5.2 vs 4.3 months) compared with placebo + carboplatin + etoposide. In fact, the overall survival period is also extended by 2 months.
Duvalliizumab (Infinefan, I drug) was approved by the FDA in March 2020 for the first line for extensive small cell lung cancer, in the CASPIAN Phase III clinical study, duvalliumab combined chemotherapy can reduce the risk of death in patients with extensive small cell lung cancer by 27%, the objective response rate increased to 68%, the median OS reached 13.0 months, achieving the longest overall survival in the history of extensive small cell lung cancer treatment.
In the latest version of the CSCO guidelines in 2022, a new domestic immune drug is recommended (level III recommendation), which is called slulizumab. In the phase III ASTRUM-005 study, the overall survival of the middle class was 15.38 months in the srullimonumab group and 11.10 months in the placebo group, and the risk of death in patients with small cell lung cancer was reduced by 38%, the 2-year overall survival rate (OSR) in the slullimonumab group was 43.2%, and the placebo group was 8.0%. In a subgroup analysis, slulizumab reduced the risk of death in patients with small cell lung cancer by 41% in Asian populations.
3. Targeted drugs
Small cell lung cancer rarely has sensitive gene mutations, so it is impossible to have more targeted drugs available like adenocarcinoma. Currently, the guidelines recommend only the multi-target anti-angiogenic drug anlotinib as a third-line and above drug recommendation.