PD-1 and PD-l1 treatment of lung cancer

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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.

What is PD-1 / L1 treatment of lung cancer?

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 is 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

What are the current PD-1 / L1 approved by the FDA for the treatment of lung cancer?

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

What are the indications for each lung cancer PD-1 / L1 approval?

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

Approved indications (lung cancer) Whether to detect PD-L1
1. Combined with pemetrexed and cisplatin / carboplatin for first-line treatment of unresectable, advanced / relapsed non-squamous non-small cell lung cancer (NSCLC) patients, regardless of PD-L1 expression no
2. Combined with carboplatin and paclitaxel / nab-paclitaxel (Abraxane) for patients with advanced / recurrent squamous non-small cell lung cancer (NSCLC) that cannot be achieved by first-line treatment, regardless of PD-L1 expression no
3. Single-agent, first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC), whose metastatic non-small cell lung cancer (NSCLC) tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%], by FDA approved test confirms that there are no EGFR or ALK genome tumor aberrations Yes, PD-L1≥50%
4. Single drug treatment for patients with metastatic non-small cell lung cancer (NSCLC), whose tumor expresses PD-L1 ((TPS) ≥ 1%), determined by FDA approved trials, disease progression after platinum-based chemotherapy Yes, PD-L1 ≥ 1%

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

Approved indications (lung cancer)
1. For the treatment of advanced (metastatic) non-small cell lung cancer that is still undergoing platinum chemotherapy
2. For the treatment of patients with advanced (metastatic) squamous non-small cell lung cancer (NSCLC), suitable for patients who have platinum-based chemotherapy or whose disease has deteriorated after chemotherapy

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

Approved indications (lung cancer)
It is used to treat locally advanced non-small cell lung cancer (NSCLC) that has not undergone surgical resection after undergoing standard platinum-based concurrent radiochemotherapy

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

Approved indications (lung cancer)
1. Metastatic non-small cell lung cancer whose condition deteriorates during or after platinum-containing chemotherapy. If the patient’s non-small cell lung cancer changes in EGFR or ALK genes, molecular targeting drugs targeting EGFR or ALK gene changes should be used first, etc. Attuzumab
2. Combined with chemotherapy (Abraxane [paclitaxel protein conjugate; nab-paclitaxel] and carboplatin) as a first-line treatment for patients with metastatic non-squamous non-small cell lung cancer (NSCLC) without EGFR or ALK

How to choose PD-1 / L1 for patients with lung cancer

How to choose the four immune checkpoint inhibitors is one of the most concerned 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

First-line immunotherapy for advanced lung cancer

Layered First-level recommendation Level 3 recommendation
PD-L1≥50% Pembrolizumab monotherapy
1% ≤PD-L1≤49% Squamous cell carcinoma: Pabolizumab

Non-squamous cell carcinoma: Pabolizumab single drug or Pabolizumab combined with platinum + pemetrexed

PD-L1 < 1% or unknown Non-squamous cell carcinoma: paclizumab combined with platinum + pemetrexed Non-squamous cell carcinoma: atezumab combined with bevacizumab combined with chemotherapy (carboplatin and paclitaxel)

Second-line immunotherapy for advanced lung cancer

Layered First-level recommendation Level 3 recommendation
No previous PD-1 / L1 treatment PD-L1 is unknown or regardless of expression status: nivolumab monotherapy PD-L1 is unknown or irrespective of expression status: atezumab monotherapy
Previous PD-1 / L1 treatment Previous PD-1 / L1 inhibitor treatment: platinum content should be combined with chemotherapy (select the appropriate chemotherapy according to histological type)

Previous PD-1 / L1 inhibitor therapy combined with chemotherapy: docetaxel or other single-agent chemotherapy (first-line unreceived drugs)

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 cel
l lung cancer with mutation

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

What indicators need to be tested before using PD-1 / L1?

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 The 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.

Can PD-1 patients with low expression use PD-1?

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 1-49% can also use K plus chemotherapy if they can tolerate chemotherapy.

Can PD-1 be used for newly treated patients with negative PD-L1 test?

Recent results of multiple PD-1 monoclonal antibody combined chemotherapy studies have proved that even if 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.

Can patients undergoing chemotherapy switch to or add PD-1?

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.

Patients who have just been diagnosed should start chemotherapy first, then choose PD-1 or use PD-1 directly after drug resistance

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.

What to do after PD-1 resistance?

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, 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, IDO inhibitor is the best treatment solutions.

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.

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