2021CSCO: New exploration of immune adjuvant and neoadjuvant therapy in NSCLC

Non-small cell lung cancer ( NSCLC ) is one of the malignant tumors with the highest mortality rate.
The tumor microenvironment in the early stage (stage I-III) of the disease can provide a favorable environment for immunotherapy , and immune checkpoint inhibitors (ICI) can recognize and kill for a long time.
Tumor cells are distinguished from cytotoxic chemotherapy, which is prone to relapse after stopping the drug.
Therefore, perioperative immunotherapy is better than chemotherapy in mechanism and can bring more benefits
.

Non-small cell lung cancer ( NSCLC ) is one of the malignant tumors with the highest mortality rate.
The tumor microenvironment in the early stage (stage I-III) of the disease can provide a favorable environment for immunotherapy , and immune checkpoint inhibitors (ICI) can recognize and kill for a long time.
Tumor cells are distinguished from cytotoxic chemotherapy, which is prone to relapse after stopping the drug.
Therefore, perioperative immunotherapy is better than chemotherapy in mechanism and can bring more benefits
.

NSCLC immunity

The presence of tumor tissues in NSCLC patients before surgery can provide a wealth of new antigens to activate the immune system, and also means better immune capabilities.
Preclinical or early studies have shown that immune neoadjuvant is superior to adjuvant therapy in eliminating metastasis
.

Neoadjuvant treatment may lead to a higher percentage of radical resections

The presence of tumor tissues in NSCLC patients before surgery can provide a wealth of new antigens to activate the immune system, and also means better immune capabilities.

According to the neoadjuvant/adjuvant immunotherapy survival data of IFCT-1601, SAKK, LCMC3, NADIM, INT0139, etc.

Figure 1 Existing survival data on neoadjuvant / adjuvant immunotherapy

FIG 1 prior neoadjuvant on immunization / survival data adjuvant therapy FIG.
1 existing on immunization neoadjuvant / survival data adjuvant therapy

Progress in neoadjuvant immunotherapy

Progress in neoadjuvant immunotherapy

The first phase III randomized controlled study of NSCLC positive neoadjuvant immunotherapy, CheckMate816, included patients with resectable stage IB-IIIA NSCLC, nivolumab (NIVO) + chemotherapy neoadjuvant therapy versus chemotherapy, the primary endpoint is primary pathological remission (pCR ^a ) Rate, the results suggest that NIVO+ chemotherapy has a good pathological remission rate in stage Ib , and it indicates that the earlier the course of the disease, the more the body can play the role of immunotherapy
.

The survival study endpoint is still under follow-up

The first phase III randomized controlled study of NSCLC positive neoadjuvant immunotherapy, CheckMate816, included patients with resectable stage IB-IIIA NSCLC, nivolumab (NIVO) + chemotherapy neoadjuvant therapy versus chemotherapy, the primary endpoint is primary pathological remission (pCR ^a ) Rate, the results suggest that NIVO+ chemotherapy has a good pathological remission rate in stage Ib , and it indicates that the earlier the course of the disease, the more the body can play the role of immunotherapy

Figure 2 The primary endpoint pCR ^a rate of CheckMate 816

FIG 2 CheckMate 816 primary endpoint the pCR ^A of FIG.
2 CheckMate 816 primary endpoint the pCR ^{A A} rate

Existing data show that PD-(L) inhibitor +/- chemotherapy neoadjuvant therapy has good safety , including adverse reactions, impact on surgical planning, surgical difficulty, and perioperative complications.
At the same time, there are more High degree of pathological tumor regression
.

Some single-arm studies reported a better progression-free survival (DFS) and overall survival (OS) of 12-24 months, while the phase III RCT study observed a pCR much higher than chemotherapy, reaching one of the preset endpoints , But the survival data is still under follow-up

Existing data show that PD-(L) inhibitor +/- chemotherapy neoadjuvant therapy has good safety , including adverse reactions, impact on surgical planning, surgical difficulty, and perioperative complications.

Research progress of adjuvant immunotherapy

The first phase III adjuvant immunotherapy study, Impower010, that reached a positive endpoint, targeted patients with completely resectable stage IB-ⅢA NSCLC, randomized after chemotherapy, one group received supportive treatment, the other group was given atilizumab, the median of the intervention group DFS was 42.
3 months, (95%CI[36.
0 NE], stratified HR=0.
79, P=0.
02), OS is still under follow-up
.

The degree of PD-L1 expression on tumor cells stained with SP263 antibody is closely related to the benefit , and patients with expression less than 1% cannot benefit

The first phase III adjuvant immunotherapy study, Impower010, that reached a positive endpoint, targeted patients with completely resectable stage IB-ⅢA NSCLC, randomized after chemotherapy, one group received supportive treatment, the other group was given atilizumab, the median of the intervention group DFS was 42.

Figure 3 Impower010's main research endpoint DFS

Figure 3 Impower010 primary endpoint DFS Figure 3 Impower010 primary endpoint DFS

Existing data show that continued PD-L1 single-agent adjuvant therapy for 1 year after complete resection and adjuvant chemotherapy has good safety and tolerability.
It has shown statistically significant DFS benefits in some patient groups, which may be related to tumor cell PD.
-L1 expression is relevant, but OS data is not yet mature
.

Existing data show that continued PD-L1 single-agent adjuvant therapy for 1 year after complete resection and adjuvant chemotherapy has good safety and tolerability.
It has shown statistically significant DFS benefits in some patient groups, which may be related to tumor cell PD.
-L1 expression is relevant, but OS data is not yet mature
.

After complete resection and adjuvant chemotherapy, continuing PD-L1 single-agent adjuvant therapy for 1 year has good safety and tolerability

Summarize

Summary summary

Immunotherapy has changed the pattern of early NSCLC treatment.
Two perioperative neoadjuvant/adjuvant immunotherapy studies, CheckMate 816 and Impower010, have reached the preliminary research endpoints, bringing hope of cure for early NSCLC patients, and more mature survival is still needed in the future The data supports this conclusion
.

At the same time, the future perioperative model still needs to continue to explore and optimize, such as population selection, alternative endpoints, treatment duration, treatment mode, etc.
We look forward to the announcement of more phase III clinical trial results
.

Immunotherapy has changed the pattern of early NSCLC treatment.
Two perioperative neoadjuvant/adjuvant immunotherapy studies, CheckMate 816 and Impower010, have reached the preliminary research endpoints, bringing hope of cure for early NSCLC patients, and more mature survival is still needed in the future The data supports this conclusion
.
At the same time, the future perioperative model still needs to continue to explore and optimize, such as population selection, alternative endpoints, treatment duration, treatment mode, etc.
We look forward to the announcement of more phase III clinical trial results
.

The content is organized from:

The content is organized from:

New exploration of immunoadjuvant and neoadjuvant therapy in NSCLC

New exploration of immunoadjuvant and neoadjuvant therapy in NSCLC

CSCO Non-Small Cell Lung Cancer Expert Committee

CSCO Non-Small Cell Lung Cancer Expert Committee

Fan Yang Peking University People's Hospital

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