Professor Wang Jialei: The IMpower010 study reached the primary endpoint of DFS, opening a new chapter in the adjuvant treatment of early NSCLC

*For medical professionals to read for reference only.
Atelizumab breaks the pattern of early treatment of lung cancer.
As an adjuvant treatment after surgery and chemotherapy, it significantly prolongs DFS compared to the best supportive treatment.
Its benefit lies in the positive expression of PD-L1, II -This is especially evident in the stage IIIA population
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The 2021 American Society of Clinical Oncology (ASCO) Annual Meeting will be held in the form of a web conference from June 4th to 8th.
As one of the largest and most widely-audited events in the oncology field, it aims to showcase the latest in oncology for scholars in different fields.
Frontier progress
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On this occasion, the "medical community" has the honor to invite Professor Wang Jialei from Fudan University Affiliated Tumor Hospital to give an in-depth interpretation of the IMpower010 research announced by the 2021ASCO conference
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 Professor Wang Jialei wonderful video driver in patients with early NSCLC lack of efficient gene-negative adjuvant therapy in patients with early lung cancer surgery is the preferred treatment, but after surgery, most patients will relapse and metastasis, and the later stages, the higher the risk of recurrence and metastasis [1]
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In order to reduce the risk of postoperative recurrence and metastasis, postoperative adjuvant therapy has gradually become an important part of the treatment of non-small cell lung cancer (NSCLC)
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 Professor Wang Jialei said that adjuvant chemotherapy is currently the most widely used postoperative adjuvant treatment, but the benefits that adjuvant chemotherapy can bring are very limited, and the 5-year survival rate is only increased by about 4%-5% [2-4]
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Although targeted adjuvant therapy after surgery has brought significant disease-free survival (DFS) benefits for NSCLC patients with EGFR-sensitive mutations [5], the efficacy of adjuvant therapy for NSCLC patients with negative driver genes still needs to be improved
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 Adjuvant therapy with atilizumab significantly prolongs DFS and brings new treatment options.
Unlike traditional chemotherapy and targeted therapy, immunotherapy can kill tumor cells by activating autoimmune T cells, with sustained response and controllable safety, etc.
Advantages, the application during the perioperative period of early NSCLC has gradually entered people's field of vision
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 Atelizumab has currently obtained indications for NSCLC and small cell lung cancer (SCLC) in China, including the first-line immune single-agent treatment of PD-L1 ≥50% (TC) or ＞10% (IC) metastatic NSCLC and immunity Combination chemotherapy is the first-line treatment for extensive-stage SCLC
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 IMpower010 is a randomized, open-label global multi-center phase III study in which a large number of doctors and patients in China also participated.
It evaluated postoperative adjuvant chemotherapy in patients with completely resected NSCLC, and the use of atilizumab as adjuvant therapy compared the most The efficacy and safety of the best supportive treatment (BSC), this ASCO meeting focused on reporting the DFS results of the IMpower010 study period [6]
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 Professor Wang Jialei introduced that IMpower010 study enrolled 1280 patients with stage IB (≥4 cm)-ⅢA NSCLC (according to UICC/AJCC 7th edition) with an ECOG score of 0-1 and complete tumor resection, and received a maximum of 4 patients.
Cycles of cisplatin-based chemotherapy (cisplatin combined with pemetrexed, gemcitabine, docetaxel or vinorelbine), of which 1005 patients were subsequently randomized to receive 16 cycles of atilizol at a 1:1 ratio Monoclonal antibody (1200 mg, once every 3 weeks) or BSC treatment
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Among the enrolled patients, 65.
6% were non-squamous NSCLC patients, 12.
2% were stage IB patients, 54.
6% were patients with PD-L1 TC≥1%, 11.
6% were EGFR mutation patients, and 3.
3% were ALK rearrangement patients
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 The primary research endpoint is the DFS assessed by the investigator, and the secondary research endpoint is the overall survival (OS), and a stratified test: First, analyze the DFS of patients with PD-L1 TC ≥ 1% (SP263 detection) stage Ⅱ-ⅢA NSCLC, Then the DFS of all randomized stage II-IIIA patients was evaluated, and then DFS analysis was performed in the intention-to-treat (ITT) population (stage IB-IIIA), and finally OS analysis was performed in the ITT population
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All randomized patients were included in the efficacy analysis
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The safety analysis was performed in all patients whose safety could be assessed, defined as patients who received ≥1 atelizumab treatment, or patients in the BSC group who received ≥1 post-baseline safety assessment
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 Figure 1.
The study design of IMpower010 After a median follow-up of 32.
8 months, for the PD-L1 TC≥1% Ⅱ-ⅢA population, the median DFS of the atilizumab group was significantly better than that of the BSC group (NE vs 35.
3 Months), significantly reducing the risk of recurrence or death, with a hazard ratio (HR) of 0.
66 (P=0.
004)
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At 24 months, the DFS rate of the atilizumab group was 74.
6%, which was higher than the 61.
0% of the BSC group; by 36 months, the DFS rates of the two groups had dropped to 60.
0% and 48.
2%, respectively (Figure 2)
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In the subgroup analysis of the PD-L1 TC≥1% Ⅱ-ⅢA population, most subgroups benefited significantly (Figure 3)
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Figure 2.
In the IMpower010 study, the DFS of the PD-L1 TC≥1% stage II-ⅢA population Figure 3.
The DFS of the key subgroup of the PD-L1 TC≥1%a stage II-IIIA population Observation of all randomized stages II-ⅢA NSCLC patients found that compared with BSC, atilizumab significantly improved patients' DFS (42.
3 vs 35.
3 months), and the hazard ratio after a median follow-up of 32.
2 months was 0.
79 (P=0.
02)
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The 36-month DFS rates of the two groups were 55.
7% and 49.
4%, respectively (Figure 4)
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The subgroup analysis of all randomized stage Ⅱ-ⅢA NSCLC showed that the level of PD-L1 was related to the benefit of DFS.
In the PD-L1 TC<1% subgroup, there was no DFS in the atilizumab group and the BSC group.
Significant difference; in the PD-L1TC≥1% subgroup, the DFS of the atilizumab group was better than that of the BSC group, and the higher the PD-L1 level, the more significant the patient benefit (Figure 5)
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 Figure 4.
DFS of all randomized phase II-ⅢA populations in IMpower010 study Figure 5.
DFS of key subgroups of all randomized phase II-ⅢA populations in IMpower010 study In this interim analysis of DFS, DFS of ITT population was not Beyond the significance boundary, the test takes longer to observe the recurrence of the disease (Figure 6)
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Similarly, as of this report, OS data is still immature, but in the PD-L1 TC≥1% stage II-IIIA population, the OS improvement trend of atilizumab can be observed (Figure 6)
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 Figure 6.
IMpower010 study ITT population (stage IB-ⅢA) DFS (left) and PD-L1TC≥1% Early OS in stage Ⅱ-ⅢA population (right) In terms of safety, Professor Wang Jialei mentioned that atelizumab The incidence of adverse events (AEs) of any grade in the group was 92.
7%, compared with 70.
7% in the BSC group; the incidence of grade 3-4 AEs in the atelizumab group was 21.
8%, and the incidence of grade 3-4 AEs in the BSC group was 11.
5%; 18.
2% of patients Atelizumab was discontinued due to AEs; the incidence of immune-mediated AEs was 51.
7% in the atelizumab group and 9.
5% in the BSC group
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No new adverse reactions were seen, and they were all clinically controllable (Table 1)
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 Table 1.
Safety summary of the IMpower010 study Professor Jialei Wang pointed out: OS has always been the "gold standard" recognized by researchers in various clinical trials, but OS data will take many years to mature, so clinicians may consider using alternative endpoints Obtain short-term data to guide clinical practice
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Because for patients and nursing staff, regardless of whether OS improves, clinically significant disease-free improvement is also beneficial
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In the field of postoperative adjuvant therapy, a number of adjuvant therapy drugs have been approved by the FDA based on their DFS benefits [7-9], suggesting that DFS can be used as a reference value for clinically meaningful endpoints (Table 2)
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 Table 2.
A number of studies focused on biomarker detection with DFS as the primary endpoint, and optimized the overall management of early patients.
Finally, Professor Wang Jialei also said that for patients with early resectable stage II-IIIA NSCLC, the IMpower010 study did not observe atiride The benefits of bilizumab in EGFR-positive, ALK-positive and PD-L1 negative patients, therefore, early use of standard genetic testing is very important to screen suitable patients, such as EGFR, ALK and PD-L1 testing
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At the same time, early intervention of lung cancer is also conducive to the long-term survival of patients.
Improving the rate of early diagnosis and early screening of lung cancer is essential for better overall management of lung cancer patients
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Expert profile Professor Wang Jialei, Deputy Director, Department of Oncology, Thoracic Section Specialist, Fudan University Cancer Hospital, Chief Physician, Master's Tutor, Deputy Director, Fudan University Thoracic Tumor Institute, Deputy Director, Youth Committee, Chinese Anti-Cancer Association Clinical Chemotherapy Committee, Shanghai Member of the Lung Cancer Professional Committee of the Association of Women Physicians, Member of the Standing Committee of the Pulmonary Tumor Professional Committee of the Chinese Medical Education Association, Vice Chairman of the Professional Committee of the Pan-Yangtze River Delta Thoracic Tumor Federation Member of the Standing Committee of the Professional Committee of Brain Metastasis of the Association Member of the Standing Committee of the Shanghai Anti-Cancer Association Committee of Cancer Rehabilitation and Palliative Care (CRPC) Member of the Committee of Thoracic Oncology of Shanghai Anti-Cancer Association Member of the Committee of Lung Cancer Molecular Targeting and Immunology of Shanghai Anti-Cancer Association Cancer Society Youth Director, MD Anderson Cancer Center Visiting Scholar Reference Materials: [1] Chinese Anti-Cancer Association Lung Cancer Professional Committee, etc.
Chinese Medical Journal, 2021, 101(16): 1132-1142.
[2] Pignon JP, et al .
J Clin Oncol 2008;26:3552-9.
[3] Postmus PE, et al.
Ann Oncol 2017;28(suppl4):iv1-21.
[4] Vansteenkiste J, et al.
Ann Oncol2019;30(8) :1244-53.
[5] Wu YL, et al.
N Engl J Med 2020;383:1711-23.
[6] Wakelee et, al.
ASCO 2021, Abstract 8500.
[7] https:// .
gov/news-events/press-announcements/fda-approves-first-adjuvant-therapy-most-common-type-lung-cancer[8] https:// https:// information-approved-drugs/fda- approves-ado-trastuzumab-emtansine-early-breast-cancer* This article is only used to provide scientific information to medical professionals and does not represent the views of this platform