A breakthrough in lung cancer immune neoadjuvant, CheckMate-816 achieves the dual endpoints of EFS and pCR, opening a new model for early-stage lung cancer treatment!

*Read only for medical professionals Reference CheckMate-816 Study EFS Data Revealed! At the just-concluded 2022 American Association for Cancer Research (AACR) annual meeting, CheckMate-816, a phase III study of nivolumab combined with chemotherapy in neoadjuvant treatment of resectable non-small cell lung cancer (NSCLC), announced the primary endpoint of event-free survival.
The results showed that the use of three courses of Opdivo combined with chemotherapy before surgery reduced the risk of disease progression, recurrence or death by 37%, and the trend of early benefit of patients' overall survival was obvious
.

As the first and currently the only immunological neoadjuvant phase III clinical study to achieve positive results in stage IB-IIIA resectable NSCLC, CheckMate-816 is also expected to achieve this result
.

As early as last year's AACR, the data of another primary endpoint of CheckMate-816, pathological complete remission (pCR), took the lead in creating a "highlight moment"
.

The results confirmed that immune neoadjuvant increased the pCR rate by more than 11 times compared with chemotherapy alone (24% vs 2.
2%)
.

CheckMate-816 demonstrated that immune-based combination therapy can significantly improve pCR and EFS in NSCLC patients in the neoadjuvant stage, and demonstrate long-term survival benefits on top of short-term benefits
.

To this end, we specially invited Professor Jiang Tao, director of thoracic surgery at Tangdu Hospital of Air Force Military Medical University, to conduct an in-depth interpretation of the research results
.

Expert Profile Professor Jiang Tao, M.
D.
, M.
D.
, Ph.
D.
Supervisor Member of Thoracic Surgeons Branch of Chinese Medical Doctor Association Director of Chinese Branch of International Society of Esophageal Diseases (CSDE) Director of the first council of Xi'an Anti-Cancer Association (and chairman of Thoracic Oncology Professional Committee) Vice Chairman of Shaanxi Anti-Cancer Association Rare Tumor Professional Committee Shaanxi Vice Chairman of the Professional Committee of Esophageal Cancer of the Provincial Anti-Cancer Association Vice Chairman of the Professional Committee of Lung Cancer of the Anti-Cancer Association of Shaanxi Province Vice Chairman of the Professional Committee of Tumor Metastasis of the Anti-Cancer Association of Shaanxi The silver award of the Chinese People's Liberation Army Military Academy's Talent Education Award, the first prize of Shaanxi Provincial Science and Technology Award, and the first prize of science and technology in Shaanxi Province Can effectively identify tumor cells
.

For PD-1/PD-L1 inhibitors, the effective presentation of tumor antigens is required to recognize and kill tumor cells, and since there are a large number of tumor cells in the primary tumor of the patient before tumor resection, it is just right to use more High tumor load to activate immune T cells [1], to achieve the purpose of shrinking tumors
.

At the same time, the risk of disease recurrence and metastasis is reduced by removing cryptic micrometastases
.

Therefore, based on the unmet needs of high postoperative recurrence and high mortality, and the unique mechanism advantages of immunotherapy in the neoadjuvant stage, immune neoadjuvant has become a research hotspot in recent years
.

Many researchers have proposed that immune neoadjuvant therapy may bring greater survival benefits, and this idea has also been confirmed by CheckMate-816, the first immune neoadjuvant phase III clinical study with positive results in NSCLC
.

Highlights continue, CheckMate-816 helps NSCLC immune neoadjuvant set sail CheckMate-816 is a randomized, open-label, multicenter Phase III clinical study to evaluate the combination of nivolumab and platinum Efficacy of dual-agent chemotherapy for neoadjuvant therapy in patients with resectable stage IB to IIIA NSCLC, regardless of tumor PD-L1 expression levels
.

The study included 358 patients who were randomized to receive nivolumab 360 mg plus platinum-containing doublet chemotherapy (every 3 weeks for a total of 3 cycles) or platinum-containing doublet chemotherapy alone (every 3 weeks) before surgery.
, a total of 3 courses)
.

The pCR increased by more than ten times, bringing a breakthrough in the efficacy of patients with operable lung cancer.
The pCR data, the primary endpoint of the study published at the AACR last year, showed that 24% of the patients in the immune neoadjuvant group achieved pCR, compared with only 2.
2% of the patients in the chemotherapy alone group.
%[2]
.

Compared with the chemotherapy group, the pCR rate of the immune neoadjuvant group increased by nearly 11 times
.

CheckMate-816 pCR results The exploratory analysis of pCR status and EFS on the AACR showed that there was a close correlation between pCR and EFS.
Not reached and 26.
6 months, respectively (HR=0.
13, 95%CI: 0.
05-0.
37)
.

The EFS results of CheckMate-816 based on pCR status, Professor Tao Jiang said: "pCR is one of the early efficacy evaluation indicators for NSCLC patients receiving neoadjuvant therapy
.
The
24% pCR of CheckMate-816 immune neoadjuvant allows us to initially see that NSCLC patients can pass Benefit from neoadjuvant chemotherapy combined with immunotherapy
.

The exploratory analysis of EFS based on pCR status also surprised us to see that pCR and EFS are closely related, which means that if the pCR rate is high in neoadjuvant therapy, it is likely to bring good EFS results, which is also positive is what we expected
.

"The risk of recurrence, progression and death is reduced by 37%, creating a new height of benefit for the whole population.
At this AACR annual meeting, EFS data, another primary endpoint of the CheckMate-816 study, was announced
.

The results showed that compared with chemotherapy alone, Preoperative nivolumab combined with chemotherapy significantly improved the patients' EFS and reduced the risk of disease recurrence, progression, or death by 37% (HR 0.
63; 97.
38% CI: 0.
43-0.
91; P=0.
0052 )
.

The median EFS was 31.
6 months (95% CI: 30.
2-not reached) in the mAb plus chemotherapy arm and 20.
8 months (95% CI: 14.
0-26.
7) in the chemotherapy alone arm
.

CheckMate-816 EFS results are noteworthy Interestingly, the subgroup analysis of the CheckMate-816 study showed that nivolumab combined with chemotherapy could benefit EFS regardless of PD-L1 expression level, disease stage, and histological type
.
Patients with ≥1
% (HR = 0.
41), stage IIIA patients (HR = 0.
54) and non-squamous carcinoma patients (HR = 0.
50) had more significant relative benefit
.

The monoclonal antibody-based therapy significantly improves the long-term prognosis of patients with operable lung cancer, and is not limited by population characteristics, achieving the benefit of the whole population
.

Although the current survival data are immature, the 2-year OS rate in the immunocombination chemotherapy group reached 83% (compared to 71% in the chemotherapy group), proving that a good overall survival (OS) early benefit has been observed in the immunoneoadjuvant therapy group condition (HR 0.
57; 99.
67% confidence interval [CI]: 0.
30-1.
07), which has the potential to improve long-term outcomes in patients with operable lung cancer in the future
.

Prof.
Jiang Tao, who analyzed the OS interim analysis of CheckMate-816 study, pointed out: "From the overall results, we are very pleased to see that the EFS in the immunocombination chemotherapy group was the same regardless of the patient's PD-L1 expression level, tumor histological type, and disease stage.
Effective improvement has been achieved
.

Although the current OS data is immature, we also expect that the benefit of EFS can eventually be translated into the benefit of OS
.

In addition, in the CheckMate-816 study, Chinese patients accounted for 1/4, I also look forward to the analysis results of the Chinese subgroup to bring more surprises
.

"The safety is well-documented, and the safety data released this time for comprehensive escort surgery show that the nivolumab combined with chemotherapy group and chemotherapy group3 - Similar rates of grade 4 treatment-related adverse events (34% vs 37%), similar rates of surgery-related grade 3-4 adverse events (11% vs 15%), and treatment-related mortality rates were 0% and 2%, respectively
.

The safety of immune neoadjuvant therapy was consistent with previous research reports, and no new safety signals were observed
.

Surgical outcomes data presented at the 2021 American Society of Clinical Oncology (ASCO) annual meeting showed [3] that a total of 94% of patients in the nivolumab plus chemotherapy group completed 3 cycles of neoadjuvant therapy, while the chemotherapy group completed 3 cycles of neoadjuvant therapy.
The completion rate is 85%
.

After neoadjuvant therapy, the rate of radical surgery in the nivolumab-chemotherapy group was 83%, which was higher than that in the chemotherapy group (75%)
.

For advanced stage IIIA patients, the nivolumab-chemotherapy group had an 83% surgery rate, which was also higher than the chemotherapy group's 72%
.

This means that the combination of nivolumab on the basis of chemotherapy will not delay or affect subsequent surgical treatment, but instead improves the chances of patients receiving radical surgery and has a positive effect on the prognosis of early-stage patients
.

FDA Approved + NCCN Guidelines, Immune Neoadjuvant Bright Sword Clinical Practice in NSCLC Based on the Results of the CheckMate-816 Study, On March 4, 2022, the U.
S.
Food and Drug Administration (FDA) approved nivolumab 360 mg in combination with platinum doublet Chemotherapy (every 3 weeks for a maximum of 3 cycles) is used as neoadjuvant therapy for adult patients with resectable NSCLC with tumors ≥4 cm or node-positive disease, regardless of PD-L1 expression levels
.

This approval is an important turning point for the NSCLC diagnosis and treatment pattern, which indicates that the combination of immunotherapy and chemotherapy has officially entered the field of neoadjuvant therapy
.

NCCN guidelines recommend the 2022 3rd edition of NSCLC The National Comprehensive Cancer Network (NCCN) guidelines for NSCLC are also recommended for neoadjuvant treatment strategies - nivolumab 360 mg combined with platinum-containing doublet chemotherapy (every 3 weeks course of treatment) , up to 3 courses) as a preoperative systemic therapy [4]
.

Professor Jiang Tao pointed out: "For the treatment of patients with resectable NSCLC, this FDA approval is an important turning point.
Combined with the recommendations of the NCCN guidelines, we can see that a completely new treatment model has emerged that is completely different from the past.
This is an event that our clinicians have been looking forward to for a long time, and it is of great breakthrough significance for clinical diagnosis and treatment
.

" Pointing the sword ahead, writing a new chapter of NSCLC neoadjuvant therapy At the end of the interview, Professor Jiang Tao shared: "The diagnosis and treatment of early tumor patients The goal of treatment is to reduce or prevent recurrence while striving to achieve clinical cure
.

However, the traditional chemotherapy regimens in the past have very limited survival benefits in neoadjuvant therapy and adjuvant therapy
.

This result also puts our surgeons and medical oncologists at a bottleneck in the pursuit of long-term survival for patients with operable NSCLC
.

The results of the CheckMate-816 study offer hope for the treatment of such patients
.

From a short-term perspective, patients can improve the chance of successful surgical treatment through neoadjuvant immunotherapy combined with chemotherapy, while preserving lung function to a greater extent and improving the quality of life of patients
.

From the perspective of long-term goals, neoadjuvant immunotherapy combined with chemotherapy reduces the risk of disease recurrence, progression and death in patients, and OS also shows a positive trend of early benefit.
We also expect this treatment regimen to eventually bring long-term benefits to patients.
survive
.

In the future, we also look forward to screening more relevant biomarkers to make neoadjuvant therapy more targeted
.

The emergence of new treatment options is often premised on clinical needs, and is gradually explored under the guidance of clinical needs to make the treatment more accurate, more effective, and more economical, so that patients suffer less and accompany less training.
This is the ultimate pursuit of our clinicians.
goal
.

"Reference: [1] Uprety D, Mandrekar SJ, Wigle D, Roden AC, Adjei AA et al.
Neoadjuvant Immunotherapy for NSCLC: Current Concepts and Future Approaches [J].
J Thorac Oncol.
2020 Aug;15(8): 1281-1297.
[2]Forde PM, Spicer J, Lu S, et al.
Abstract CT003: Nivolumab (NIVO)+ platinum-doublet chemotherapy (chemo) vs chemo as neoadjuvant treatment (tx) for resectable (IB-IIIA) non -small cell lung cancer (NSCLC) in the phase 3 CheckMate 816 trial[J].
Cancer Res (2021) 81 (13_Supplement): CT003.
[3]Spicer J, Wang C, Tanaka F, et al.
Surgical outcomes from the phase 3 CheckMate 816 trial: Nivolumab (NIVO)+ platinum-doublet chemotherapy (chemo) vs chemo alone as neoadjuvant treatment for patients with resectable non-small cell lung cancer (NSCLC)[J].
Journal of Clinical Oncology 2021 39:15_suppl, 8503-8503[4] NCCN NSCLC Guidelines Version 3.
2022*This article is only used to provide scientific information to medical professionals and does not represent the views of this platform