Professor Han Baohui: Atelizumab is expected to become a new choice for the first-line treatment of advanced non-small cell lung cancer

*Only for medical professionals to read and reference IMpower110 research data and then update! Professor Han Baohui will explain it for you! PD-1/L1 inhibitors have rewritten the pattern of non-small cell lung cancer (NSCLC) treatment.
Among them, the PD-L1 inhibitor atelizumab has been approved by the U.
S.
Food and Drug Administration (FDA) with the success of the IMpower110 study Atilizumab is the first-line treatment for patients with metastatic NSCLC with high PD-L1 expression (TC≥50% or IC≥10%) [1].

This indication is expected to be launched in China, providing a new option for the treatment of NSCLC patients with high PD-L1 expression in my country.

The "medical community" sincerely invites Professor Han Baohui from the Chest Hospital of Shanghai Jiaotong University to study and interpret the performance of atilizumab in the first-line treatment of the IMpower110 study, and to teach the clinical practice experience of immunotherapy in the Chinese population.

Atilizumab revolutionizes the first-line immunotherapy pattern of NSCLC.
There are a variety of PD-1/L1 inhibitors approved for first-line treatment indications at home and abroad, but most of the approved indications for drugs are combined chemotherapy, and only atelix Three drugs, Lizumab, Pembrolizumab and Cemiplimab, have been approved as a single agent for the treatment of patients with high PD-L1 expression.
Among them, atilizumab is currently the only PD-L1 inhibitor.

The success of atilizumab in the first-line treatment of lung cancer “singles” reflects the superior strength of the drug itself.
It also breaks the previous pattern of only PD-1 inhibitors in the first-line immune single-agent treatment of NSCLC.
Patients provide another powerful choice.

Atelizumab was approved for the first-line treatment of patients with PD-L1 high-expressing NSCLC.
The indication is based on the significant advantages and benefits of the IMpower110 study.The IMpower110 study is a global multi-center, randomized controlled, phase III clinical trial that compares the efficacy and safety of atilizumab and standard platinum-containing dual-agent chemotherapy as the first-line treatment.
The study was announced at the 2019 European Society of Medical Oncology (ESMO) conference.
The main results of the analysis, in patients with high PD-L1 expression (TC3/IC3-WT), the median overall survival (OS) of the atilizumab group and the chemotherapy group were 20.
2 months and 13.
1 months, respectively (HR= 0.
59, 95% CI: 0.
40-0.
89, P=0.
0106), prolonged by 7.
1 months, and reduced the risk of death by 41% (Figure 1) [2].

Figure 1.
The OS data of the PD-L1 high-expressing population in the IMpower110 study.
The relevant data of the IMpower110 study at the 2020 World Lung Cancer Conference (WCLC) have been updated.

Among the population with high PD-L1 expression, the median progression-free survival (PFS) of the atilizumab group and the chemotherapy group were 8.
2 months and 5.
0 months, respectively (HR=0.
59, 95%CI: 0.
43-0.
81) The objective response rate (ORR) was 40.
2% and 28.
6%, and the median duration of response (DoR) was 38.
9 months and 8.
3 months, respectively (Figure 2) [3].
The ultra-long DoR reflects the long delay of immunotherapy Tail characteristics.

Figure 2.
IMpower110 study PFS and confirmed ORR and DoR results Professor Han Baohui said: "Atelizumab is different from previous PD-1 inhibitors.
It is currently the only single-agent first-line treatment approved by the FDA for PD-L1 high Expression of PD-L1 inhibitors in NSCLC patients.

From the overall data, whether it is the main research endpoint OS, PFS, DoR, and short-term efficacy indicators ORR, etc.
, have been significantly improved, which also reflects atelizolin Antibiotics can convert short-term benefits into long-term survival benefits, which is an immunotherapy strategy that can make patients continue to benefit for a long time.

I think if atelizumab is approved as the first-line treatment of NSCLC, for clinicians, We have one more "weapon" in our hands, which will also add new options to the choice of clinical medication.

"Atelizumab has achieved excellent performance in the first-line treatment of advanced NSCLC, and extended the patient's OS to nearly 2 years.
Once remission is reached, the remission lasts for more than 3 years, and it is expected to become a PD-L1 high-expressing NSCLC patient One of the standard treatments.
The
unique mechanism and the safety advantages of PD-L1 inhibitors appear.
The side effects of lung cancer chemotherapy drugs can affect the quality of life of patients.
Today, with the rapid development of lung cancer diagnosis and treatment, patients not only need to prolong their survival, but also need high-quality survival.

And some patients have the problem of being unable to tolerate chemotherapy.
Therefore, immune monotherapy may be more friendly to patients who are concerned about the side effects of chemotherapy and cannot tolerate chemotherapy.

However, the same are immune checkpoint inhibitors (ICIs), PD-1 inhibitors and PD The adverse reactions caused by -L1 inhibitors are different.
The essence of this difference lies in the site of action and the mechanism.

PD-1 inhibitors can block the binding of PD-1 and PD-L1 at the same time.
In
contrast, PD-L1 inhibitors can retain the PD-L2 pathway, maintain a stronger autoimmune regulatory function, and reduce immune-related adverse reactions (such as immune-related pneumonia).
).
A
number of Meta analyses have shown that the incidence of adverse reactions of PD-L1 inhibitors is lower than that of PD-1 inhibitors, especially in interstitial pneumonia [4].
The
mechanism of action is PD-L1 inhibitors The safety of a more dominant position lays the foundation, and various evidence-based medical data have also confirmed the good safety of PD-L1 inhibitors.

From the safety data of the IMpower110 study report, the atilizumab group 3-4 The proportion of patients with grade-grade treatment-related adverse events (AE: 14.
3% vs 44.
9%), severe treatment-related AEs (9.
4% vs 15.
6%), and discontinuation due to AEs (7.
3% vs 17.
1%) were lower than those in the chemotherapy group [3] ( Table 1).

The safety characteristics of atelizumab single-agent therapy are consistent with the previous analysis results and the past experience of all indications, and no new or unexpected safety signals have been observed, suggesting that atelizumab Drug treatment can guarantee a good quality of life for patients.

Table 1.
Summary of IMpower110 study safety data.
Professor Han Baohui added: “When clinicians and patients have similar drug efficacy, safety may become a more important point.
Therefore, improving safety can also improve patient compliance.
, To ensure adequate and full-course medication and to ensure the efficacy and quality of life.

"Single drugs and combination programs go hand in hand, and it is necessary to accurately screen the population.
In the first-line treatment of NSCLC, immune single drugs and combination therapies show a pattern of controversy.

How to choose the most appropriate treatment plan for the patient in clinical practice to maximize the benefit of the patient? How to weigh the advantages and disadvantages of the efficacy and safety of single-drug or combined therapy? These are issues worthy of consideration by clinicians.

Professor Han Baohui said: "The consideration of specific treatment decisions is still based on the patient's individual situation-such as NSCLC patients who cannot tolerate chemotherapy, are young, are in good physical condition, and have a light tumor burden.
They can avoid the side effects of combined therapy and choose immunity.
Single-agent therapy; if the disease progresses to an advanced stage and the tumor burden is heavy, immune combination therapy is a better choice.

"For combination therapy, in addition to immune combination chemotherapy, there are still many options.

The WJOG@Be study suggested that the "de-chemotherapy" regimen of atelizumab + bevacizumab first-line treatment of advanced NSCLC patients with high PD-L1 expression has an ORR of 64.
1% and a 1-year PFS rate of 54.
9%[5 ], "Go to chemotherapy" at the same time to ensure the effective remission of the disease.

Figure 3.
The ORR of the WJOG@Be study reached 64.
1%.
Figure 4.
The results of the WJOG@Be study of PFS have adverse prognostic factors, such as patients with liver metastases at baseline, EGFR/ALK mutations and progression after TKI treatment, you can try IMpower150 IV The drug combination model improves the efficacy.

The subgroup analysis of the IMpower150 study showed that the ORR of patients with liver metastases and EGFR mutations at baseline in the four-drug combination group were 60.
8% and 70.
6%, respectively, and the four-drug combination model had OS, PFS, and DoR benefits compared with the three-drug combination (BCP) [6].

Professor Han Baohui said: “For the treatment of people with high PD-L1 expression, clinicians can choose either single drug or combination therapy.

In addition to the previous combination of immunization and chemotherapy, immunization combined with anti-angiogenesis therapy is also a potentially powerful option.
Anti-vascular drugs can improve the tumor microenvironment in mechanism, resulting in a better effect of 1+1>2.

"Future challenges, individualized treatment strategies, and the emergence of PD-1/PD-L1 inhibitors have completely subverted the treatment pattern of PD-L1-positive NSCLC patients.
However, as research explores the nature of biology and the evidence of evidence-based medicine With continuous accumulation, the future of immunotherapy still has both opportunities and challenges.
The
number of people benefiting from a single immunotherapy is limited.
How to expand the benefit group while avoiding the risk of serious immune-related adverse reactions? The immunotherapy combination program has unlimited potential.
But how do the different combination schemes correspond to the population? It is still worthy of further exploration.

Professor Han Baohui emphasized: “Whether it is a single immunization drug or a combination therapy must be more precise.
Although the immunization single drug has a light treatment burden, it benefits more from the high expression of PD-L1.
The population, this part of patients accounts for only 30% of all NSCLC patients, how to further expand the benefit population has become an urgent problem for clinicians to solve.

If a combination therapy is used, which of the different combinations is best? Who should correspond to? The accumulation of more evidence-based medical evidence is still needed.

In addition, in addition to precise screening of patients with high PD-L1 expression that can benefit from immunotherapy, it is also necessary to predict populations prone to immune-related adverse events.

Therefore, precise screening is to identify patients with good curative effects and patients who are'unsuitable'.

"I believe that with the continuous advancement of related research, immunotherapy will surely bring more new options for the diagnosis and treatment of advanced NSCLC, and create a new height in the diagnosis and treatment of lung cancer.

Expert profileProfessor Han Baohui Executive Chairman of China Lung Cancer Institute Shanghai Leading Talent and Outstanding Subject Leader Director of Respiratory Medicine Department of Shanghai Chest Hospital Deputy Director of Shanghai Thoracic Oncology Institute Ph.
D.
and post-doctoral tutor of Shanghai Second Medical University Shanghai Chest Hospital Drugs Director of the Clinical Research Institute Chairperson of the Oncology Branch of the Asia-Pacific Society of Medical Immunology; Special Allowance from the State Council; Special Allowance from the State Council; CFDA Review Expert; Chairperson of CSCO Tumor Vascular Targeting Professional Committee; Vice Chairperson of CSCO Tumor NSCLC Professional Committee; Chinese Anti-Cancer Association; National Tumor Clinical Collaboration Center Executive Member, Chinese Anti-Cancer Association, Vice Chairman, Chinese Medical Association, Respiratory Branch, Member of the Standing Committee of the Respiratory Branch of the Chinese Medical Association, Vice Chairman, Shanghai Medical Association, Vice Chairman of the Eighth Council of Shanghai Anti-Cancer Association, Vice Chairman, Chinese Physician Association Oncology Branch Standing Committee Reference: [1].
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