PD-1 and PD-l1 treatment of lung cancer

Lung cancer immunotherapy, lung cancer immunotherapy, lung cancer PD-1 treatment, and lung cancer PD-L1 treatment are all you want to know.

In the past two years, immune checkpoint inhibitors have undoubtedly been one of the most successful tumor immunotherapies, which has changed the treatment prospects for NSCLC. The four PD-1/L1 currently approved for lung cancer have improved the five-year survival rate of advanced lung cancer from less than 5% to 16%, which has tripled, and many patients and even doctors are excited. Immunotherapy is gradually becoming a “special effect” drug for the treatment of advanced non-small cell lung cancer. Most lung cancer patients still have many questions about PD-1 treatment, and today we will answer them one by one.

Immunotherapy is a therapy that uses the patient’s immune system to fight cancer. PD-1/L1 treatment is called immune checkpoint inhibitor therapy and is a type of immunotherapy.

Immune checkpoint inhibitor therapy refers to PD-1, a protein on the surface of T cells that helps control the body’s immune response. When PD-1 binds to another protein called PDL-1 on cancer cells, it prevents T cells (an immune cell) from killing cancer cells. The PD-1 inhibitor binds to PDL-1, thereby releasing the immune suppression of T cells and regaining the ability to kill cancer cells

The FDA approved four immune checkpoint inhibitors: nivolumab (O drug), pembrolizumab (K drug), atezolizumab (T drug), and durvalumab (I drug) for the treatment of non-small cell lung cancer.

Drug Name Pembrolizumab Nivolumab Attuzumab Devaruzumab

English name Keytruda Opdivo Tecentriq Imfinzi

manufacturer Merck Bristol-Myers Roche AstraZeneca

Dosage 2mg / kg once every three weeks 3mg / kg once every two weeks 1200mg once every three weeks 10mg / kg once every two weeks

Listing U.S. listing Listed in China U.S. listing Listed in China

Pabolizumab (Pembrolizumab, Pambrolizumab, Pembrolizumab) | Kerui Da (Jinheide, Keytruda) | K drug

Nivolumab (Navumab, Niluumab, Nivolumab) | Odivo (Odivo, Odvo, Opdivo) | O drug

Devarizumab (Duvaluzumab, Duvalizumab, Deluzumab, Durvalumab) | I drug (Imfinzi)

Attuzumab (Atezolizumab, Atezolizumab) | T drug (Tecentriq)

How to choose the four immune checkpoint inhibitors is one of the most concerning problems of lung cancer patients. The following tables summarize the choice of medication plan for everyone in detail and clearly.

Mutation-free non-small cell lung cancer

Third-line immunotherapy for advanced lung cancer: secondary recommendation, nivolumab.

Three-stage unresectable non-small cell lung cancer: Grade III recommendation, receiving consolidation therapy with dufaliolizumab after radiotherapy and chemotherapy.

Non-small cell lung cancer with mutation

For immunotherapy of NSCLC with positive EGFR/ALK, there is still insufficient evidence. The IMpower150 study subgroup analysis results show that the following scheme has a certain effect: atelizumab + bevacizumab + carboplatin + taxol

At present, clinicians refer to the expression of TMB and PD-L1 as markers for lung immunotherapy and chemotherapy. Rossy has compiled an article for you to interpret the five biomarkers that predict the efficacy of PD-1. You can refer to: How to predict the efficacy of PD-1 in advance? A comprehensive analysis of the five major predictors!

1) PD-L1

At present, it is considered that the expression of PD-L1 in tumor tissues is a more reasonable marker for selecting the dominant population before anti-PD-1/PD-L1 treatment. But at the same time, there are many problems in PD-L1 detection, such as spatial heterogeneity. Can a small part of the tumor represent the entire state of the entire tumor? There is also temporal heterogeneity because after treatment, PD-L1’s expression state will change. There is no standardization of immunohistochemical detection. There are multiple antibodies for PD-L1 immunohistochemical staining. The positive agreement rate of different antibodies is only 73%–76%, which will affect the detection results.

2) TMB

Current research shows that TMB / bTMB as a predictive marker for the therapeutic effect of ICIs is still controversial.

For those domestic patients who have just been diagnosed with advanced non-small cell lung cancer, the domestic lung cancer treatment industry generally recommends a PD-L1 test. If PD-L1 ≥ 50%, whether it is squamous cell carcinoma or non-squamous cell carcinoma, newly-treated, non-gene mutation non-small cell lung cancer patients can be treated with K drugs to obtain the greatest chance of survival benefit at present.

Of course, for the clinical application of immune checkpoint inhibitors, the United States is the most researched and has the richest clinical experience. The authoritative lung cancer experts in the United States are based on the current information on TMB and PD-L1 for the chemotherapy and / or immunotherapy of lung cancer Patients are stratified.

1. Anti-PD-1 monotherapy is given to patients with “hot” or inflamed tumors with high PD-L1 expression and TMB.

2. For patients with high PD-L1 expression but low TMB, give chemoimmunotherapy.

3. For those patients with high TMB but low or negative PD-L1 expression, give chemoimmunotherapy or anti-PD-1 / CTLA-4 therapy.

4. In addition, for patients with “cold” or non-inflammatory tumors with low TMB and low or negative PD-L1 expression, chemotherapy is performed with or without immunotherapy or possible cellular immunotherapy.

Rossy reminds the majority of lung cancer patients that before using PD-1, they must choose an authoritative testing company for biomarker testing, and then consult Bei Shangguang or even a well-known lung cancer expert in the United States to formulate a precise medication plan, or they can consult a global oncologist. Department of Web Medicine.

For those patients with advanced non-small cell carcinoma who have just been diagnosed, as long as PD-L1 expression is positive, whether it is squamous cell carcinoma or non-squamous cell carcinoma, it may be possible to obtain survival benefits from the initial treatment of K-drug monotherapy, thereby extending life. Some experts also suggest that patients with PD-L1 expression between 1% and 49% can also use K plus chemotherapy if they can tolerate chemotherapy.

Recent results of multiple PD-1 monoclonal antibody combined chemotherapy studies have proved that even if the PD-L1 test is negative, or PD-L1 is not tested conditionally, PD-1 monoclonal antibody combined with chemotherapy can treat squamous cell carcinoma or non-squamous cell carcinoma. Cellular lung cancer patients bring more significant survival benefits with chemotherapy alone.

For patients with PD-L1-negative non-small cell lung cancer, regardless of whether they have squamous or non-squamous non-small cell lung cancer, if they have not received chemotherapy before, after receiving K combined chemotherapy, compared with chemotherapy alone All patients can get a longer survival benefit. Such data is good news for those patients with negative PD-L1 expression or no condition to detect PD-L1.

Regardless of whether it is squamous or non-squamous non-small cell lung cancer, the effect of K combined with chemotherapy is definitely better than chemotherapy alone, but can patients who are receiving chemotherapy receive PD-1 monoclonal antibody? What is the better effect of chemotherapy?

After radiotherapy and chemotherapy, it will kill some tumor cells, thereby releasing tumor antigens and stimulating human immunity. At this time, if PD-1 monoclonal antibody treatment is given, theoretically, the anti-tumor effect will be stronger. At present, there are preliminary research results that show that the immune maintenance treatment of PD-1 monoclonal antibody or PD-L1 monoclonal antibody after simultaneous radiotherapy and chemotherapy has a good effect and significantly prolongs life.

For those patients with advanced non-small cell cancer who have just been diagnosed, early use of PD-1 monoclonal antibody will bring better survival benefits than late use.

Patients with effective PD-1 inhibitors generally have long-lasting effects; however, about 30% of patients have been observed to have disease resistance. The key to overcoming drug resistance is mainly two points:

First, if possible, a biopsy and in-depth immune analysis can be performed on newly added or increasing drug resistance sites to find the cause of drug resistance and treat according to the cause. For example, some patients are due to compensatory high expression of TIM-3, LAG-3, or IDO; then choose PD-1 inhibitor combined with TIM-3 inhibitor, LAG-3 antibody, or IDO inhibitor as the best treatment solution.

Secondly, for patients who cannot determine the cause of drug resistance, they can combine the specific conditions to choose the best joint partner to reverse drug resistance and prolong survival or switch to traditional treatments such as radiotherapy and chemotherapy, intervention, radio frequency, and particle implantation.

Finally, and most importantly, more and more evidence supports that immunotherapy, such as PD-1 inhibitors, should be used as early as possible when the patient’s general condition is better and the tumor burden is relatively small.