Surgery is the preferred treatment option for most patients with early- and mid-stage non-small cell lung cancer, but patients are often at high risk of recurrence after surgery. To reduce this risk, physicians may supplement radiotherapy before and after surgery, which is called “neoadjuvant therapy” before surgery and “adjuvant therapy” after surgery.
In recent years, the rise of immunotherapy has extended the lives of many patients with advanced lung cancer. The most effective drugs for lung cancer are a large class of drugs called “immune checkpoint inhibitors,” including the familiar nabolutumab (commonly known as “O”), pablizumab (commonly known as “K”), and atezumab (commonly known as “K”). The drugs are known as “immune checkpoint inhibitors” and include familiar drugs such as nabolutumab (commonly known as “O”), pablizumab (commonly known as “K”), and atezolizumab, which enhance the body’s immune response to cancer cells and make them invisible.
So when immunotherapy “moves forward” to neoadjuvant therapy, will it do any good? Although early-stage neoadjuvant immunization is still in early trials, preliminary results have shown good promise.
Is the use of immunotherapy before surgery, effective?
Current clinical studies have found that the use of nabritumomab and atezumab before surgery not only did not delay surgery, but also improved the success of surgery, allowing more patients to achieve complete tumor resection. In addition pathological assessment based on post-treatment surgical resection specimens showed that preoperative immunotherapy better induced a killing effect on tumor cells, while the presence of a large number of infiltrating T lymphocytes in the lesions of such patients may predict longer survival in this group of patients. Let’s look at the specific data:
Navulizumab
A study at Johns Hopkins School of Medicine included 21 stage I-IIIA lung cancer samples, all of which were treated with nabugliumab before surgery, and found that more than 95% achieved “R0 resection”. 45% of patients achieved “pathologically significant remission (MPR) The results showed that more than 95% achieved “R0 resection” and 45% achieved “significant pathological remission (MPR),” meaning that less than 10% of the tumor cells were in the excised mass sample.
Atezolizumab
In one study:: 21 patients with stage IB to IIIB lung cancer who were treated preoperatively with atezolizumab achieved pathologically significant remission in 22% and even pathologically complete remission (pCR) in 7%, meaning that no cancer cells were observed microscopically, and this group of patients was found to have a low overall risk of recurrence in other previous tumor types.
Is immunotherapy better compared to neoadjuvant radiotherapy?
In non-small cell lung cancer, neoadjuvant radiotherapy has been used clinically for more than a decade and has a more definite efficacy. The combination of radiotherapy and chemotherapy is the most effective, with stage III patients receiving neoadjuvant radiotherapy + lobectomy having a median survival time of 34 months and 36% of patients surviving longer than 5 years . However, the combination of radiotherapy and chemotherapy also has greater side effects, and in addition some randomized controlled studies have shown that neoadjuvant chemoradiotherapy is not more effective; therefore, neoadjuvant chemotherapy is the most commonly used in clinical practice.
Neoadjuvant immunotherapy has not been tried for long, and authoritative data on survival are lacking. In addition, it works differently from radiotherapy and requires a unique metric, the “pathologically significant remission” rate, to evaluate its efficacy, which cannot be directly compared with radiotherapy. Therefore, it is difficult to determine which neoadjuvant treatment option is more advantageous.
Immunotherapy versus chemotherapy
Is it possible to combine immunotherapy with chemotherapy?
There are studies that have shown that the combination of immunotherapy and chemotherapy is a good combination.
One study confirmed that preoperative use of nabulizumab in combination with chemotherapy resulted in a pathologically significant remission rate of 80% in 30 patients with stage I-IIIA lung cancer [and that preoperative treatment with atezumab + chemotherapy (carboplatin + albumin-bound paclitaxel) was successful in 78% of 18 patients with stage IB-IIIA, with a pathologically significant remission rate of 50%, of which 21% achieved complete remission (microscopic cancer cells could not be found completely).
It is clear that preoperative application of immunotherapy in combination with chemotherapy is more effective than one alone. However, both of these studies had low sample sizes and less convincing results. The results of the LCMC3 study, which was just published by ASCO this year, showed an overall pathological deep remission rate of 18% with neoadjuvant atezumab, which is the largest clinical trial of neoadjuvant immunotherapy with the largest sample size available, and the data can be used as a reference.
A combination of two immunotherapy drugs, is it feasible?
Ipilimumab is another new immunotherapy agent that is often combined with nabulizumab for the treatment of advanced malignancies, and there is only one Checkmate227 study in advanced lung cancer that has explored the value of its combination modality in the first-line treatment of lung cancer. In early-stage lung cancer, one of these studies combined nabulizumab + Ipilimumab preoperatively in patients with stage I-IIIA lung cancer, with 33% of patients achieving deep pathologic remission and better overall response rates than nabulizumab alone, but also significantly higher toxicity, with nearly 20% of patients in the combination group unable to undergo surgery due to drug toxicities and disease progression.
Summary
While neoadjuvant immunotherapy is still in the exploratory phase, current data show that both single-agent and combination with chemotherapy significantly improve overall response compared with conventional chemotherapy without significant side effects.