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Professor Wang Jie gave an in-depth interpretation of IMpower010 Asian data update
Adjuvant chemotherapy is the standard postoperative treatment for patients with early-stage NSCLC, but the 5-year OS rate is only about 5% [1], and the clinical benefit is very limited. At the 2021 ASCO Annual Meeting, the disease-free survival (DFS) data of the IMpower010 study were presented for the first time, confirming that adjuvant immunotherapy can bring significant clinical benefits to patients in the early postoperative period, and at the same time opening a new era of perioperative immunotherapy for resectable NSCLC. With the extension of follow-up time, the IMpower010 study continues to deliver exciting long-survival results: at the global median follow-up of the global population at 4 years, the 5-year OS rate of PD-L1 TC≥1% patients with stage II-IIIA was 76.8%, and the 5-year OS rate of patients with PD-L1 TC≥50% and patients with stage II-IIIA was as high as 84.8%. Based on the excellent efficacy and safety data of the IMpower010 study, atezolizumab was approved by the FDA and NMPA in 2021 and 2022 respectively for the adjuvant treatment of patients with stage II-IIIA NSCLC after PD-L1 positive, surgical resection, and platinum-containing chemotherapy, which also makes it the first and only immunotherapy drug approved for postoperative adjuvant therapy in NSCLC patients in China. In the 2023 Chinese Society of Clinical Oncology (CSCO) guidelines for the diagnosis and treatment of NSCLC, atezolizumab became the only adjuvant immunotherapy drug that received a level I recommendation. The National Comprehensive Cancer Network (NCCN) NSCLC guidelines and the American Society of Clinical Oncology (ASCO) NSCLC guidelines recommend atezolizumab as adjuvant therapy for resectable NSCLC.
At the 2022 Japanese Society of Medical Oncology (JSMO) Annual Meeting, the DFS data from the IMpower010 study in Asian populations were presented, suggesting that the DFS benefits in Asian populations are consistent with those in global populations. However, whether the DFS benefit in the Asian population can also translate into OS benefit is still a major clinical concern. In anticipation, the 2024 American Association for Cancer Research (AACR) Annual Meeting ushered in the update of the OS data of the IMpower010 study in Asian populations, and the "medical community" specially invited Professor Wang Jie from the Cancer Hospital of the Chinese Academy of Medical Sciences to analyze the updated data in depth.
The updated OS data in the Asian population once again confirmed the excellent efficacy of adjuvant atezolizumab therapy
The Asian ITT population in the IMpower010 study included a total of 233 patients from Chinese mainland, Japan, South Korea, Hong Kong, and Taiwan, accounting for 23.2% of the total population, and the baseline characteristics in the PD-L1 TC≥1% Asian population were generally consistent with those in the PD-L1 TC≥1% global population in the stage II-IIIA population.
Figure 1 IMpower010 study design
Previous interim analysis of DFS in Asian populations showed [2,3]:
- The median DFS of Asian patients with PD-L1 TC≥1% of patients with stage II-IIIA NSCLC was 42.3 months versus 31.4 months in the BSC arm with atezolizumab (HR=0.63), and the median DFS atezolizumab arm was 35.3 months versus 35.3 months in the BSC arm (stratified HR=0.66) in the Asian population.
Fig. 2 DFS and OS data of the PD-L1 TC≥1% Asian patients with stage II-IIIA
- PD-L1 TC ≥ 1% of Asian patients with stage II-IIIA disease, and atezolizumab versus BSC reduced the risk of death by 27%, consistent with global data (HR=0.71).
The safety profile is consistent with previous data and controllable, and adjuvant atezolizumab can help patients survive long and ensure drug safety
■ In terms of safety, the safety profile of the Asian population (n=229) for evaluable safety was consistent with that of the global population. Grade 3-4 adverse events of special interest (AESIs) in Asian populations included hepatitis (4.9%), hypothyroidism (2.5%), rash (0.8%), adrenal insufficiency (0.8%), pneumonia (0.8%), and enteritis (0.8%). The overall adverse reactions in the Asian population were clinically controllable, and no new or unexpected safety signals were observed.
Fig. 3 Safety data in Asian populations
Overall, combined with the data from the interim DFS analysis of the Asian population and the updated data of OS, the benefit and risk characteristics of atezolizumab in the 1% of Asian patients with stage II-≥IIIA stage II-IIIA NSCLC after complete resection and adjuvant chemotherapy were clarified, and the DFS benefit in the Asian population was successfully translated into the benefit of OS, which fully supported the status of adjuvant atezolizumab as the clinical standard of care (SOC).
Perioperative immunotherapy brings long-term survival after surgery, and the treatment mode is three-pronged, but the choice of treatment mode still needs to be optimized
In terms of mechanism, adjuvant immunotherapy targets the small residual lesions of tumors in postoperative patients, inhibits tumor recurrence, and further prolongs the survival of patients with early-stage lung cancer. The IMpower 010 study confirmed that the long-term survival of patients with PD-L1 TC≥1% of patients with stage II-IIIA was 76.8% after surgery, and the 5-year OS rate of PD-L1 TC≥1% patients with stage II-IIIA was 76.8%, and the 5-year OS rate of patients with PD-L1 TC≥50% and 54.8% for patients with stage II-IIIA was 84.8%, bringing hope for a cure to patients and officially opening a new chapter in the immunotherapy of resectable NSCLC.
Subsequently, the neoadjuvant therapy mode and the perioperative sandwich cake treatment mode in the perioperative immunotherapy of resectable NSCLC have also been continuously consolidating the evidence of survival benefit in the past two years of clinical studies, and the immunoneoadjuvant therapy represented by the CheckMate 816 study and the perioperative sandwich cake immunotherapy represented by the KEYNOTE-671 study have obtained positive results for EFS. While the clinical treatment options are becoming more and more abundant, "how to choose the appropriate perioperative immunotherapy mode for the right patient" has become a hot topic of clinical discussion today.
Surgery is still the curative treatment for patients with perioperative NSCLC. In phase III clinical studies of both neoadjuvant immunotherapy and sandwich cake immunotherapy, we observed that approximately 20 percent of patients [4-9] lost the opportunity for surgery due to adverse reactions (AEs), disease progression (PD), or other reasons. In the CheckMate 816 study, we found that patients who lost the opportunity for surgery had a worse prognosis [10]. In order to avoid the loss of the opportunity for radical surgery as much as possible, it is recommended that the patient's related risk factors, surgical feasibility and other clinical conditions should be carefully evaluated during the MDT process, and patients with PD-L1-positive stage II-IIIA should be treated with immunoadjuvant therapy after surgery.
In the era of precision cancer therapy, the status of tumor biomarkers has become an important consideration in diagnosis and treatment decisions. NCCN guidelines [11] recommend testing for PD-L1 status, EGFR mutations, and ALK rearrangements in patients with stages IB-IIIA, IIIB [T3, N2] prior to initiation of neoadjuvant immunotherapy and adjuvant immunotherapy.
In clinical studies of neoadjuvant immunotherapy and perioperative sandwich cake immunotherapy, the survival benefit of PD-L1-positive individuals was significantly superior to that of PD-L1-negative patients [4-9]. The importance of preoperative PD-L1 testing is self-evident. However, preoperative biopsy may face clinical problems such as limited tissue sample size and increased patient communication costs. On the other hand, adequate tumor tissue samples can usually be obtained for biomarker testing after surgery, and adjuvant immunotherapy with atezolizumab can be given to postoperative patients with PD-L1 positive stage II-IIIA NSCLC. For patients with EGFR-positive postoperative NSCLC, the ADAURA study also reinforces the clinical evidence for adjuvant osimertinib therapy (ADAURA: 5-year OS rate of 85% for patients with EGFR mutation stage II-IIIA, HR=0.49). In 2023, ESMO presented unprecedented data from the ALINA study of adjuvant therapy for ALK fusion-positive NSCLC [ALINA: Adjuvant alectinib in patients with completely resected IB (tumor≥4 cm) to stage IIIA ALK-positive NSCLC reduced the risk of disease recurrence or death by 76% (DFS HR=0.24, p.). <0.0001）]。 It is the future clinical development trend and direction to bring new treatment options for patients with resectable ALK+ NSCLC, and to provide accurate treatment plans for different types of patients according to the detection status of tumor markers in perioperative NSCLC patients.
The exploration of treatment modalities for patients with perioperative NSCLC is continuing, which requires not only evidence from large-scale clinical studies, but also real-world data, including patient efficacy and safety. Patients with early-stage lung cancer have higher expectations of "life", so the factors that clinicians need to consider in the treatment of these patients are more complex. The white robe is the weight of life, and the belief in precision and individualized treatment is an important vane for future progress. IMpower010 has drawn a complete chain of clinical evidence for the adjuvant immunotherapy model for lung cancer patients around the world, and its efficacy and outstanding safety profile have also brought a stable postoperative life to many postoperative patients, and we expect that more different types of patients will benefit from diversified treatment modalities in the future with the passage of time.
Expert Profile
Prof. Jie Wang
- Director of the Department of Internal Medicine, Cancer Hospital, Chinese Academy of Medical Sciences
- Chief Physician, Tenured Professor and Doctoral Supervisor of Peking Union Medical College
- Winner of the 2021 Ho Leung Ho Lee Foundation Science and Technology and Progress Award
- Winner of the National "Outstanding Young Scholars" Fund
- Leader of the innovation team of the Ministry of Education
- Winner of the 7th China Young Women Scientist Award
- He was selected into the National Millions of Talents Project and won the title of young and middle-aged experts with outstanding contributions
- Vice President of the Chinese Society of Clinical Oncology (CSCO).
- Vice Chairman of the CSCO Small Cell Lung Cancer Expert Committee
- Candidate Chairman of the CSCO Expert Committee on Non-Small Cell Lung Cancer
- Chairman of the Multidisciplinary Oncology Committee of the Chinese Medical Doctor Association
- Vice Chairman of the Lung Cancer Committee of the Chinese Anti-Cancer Association
- Vice Chairman of the Oncology Branch of Beijing Medical Association
- Vice President of Beijing Research Institute for Chronic Disease Prevention and Health Education
Bibliography:
[1] Xu Yuanyuan, Mao Feng, Chen Xiaoke, et al.Research progress of perioperative immunotherapy for non-small cell lung cancer[J/OL].Chinese Journal of Clinical Thoracic and Cardiovascular Surgery:1-12[2024-04-02].http://kns.cnki.net/kcms/detail/51.1492.R.20240320.1529.004.html.
[2] Felip E, Altorki N, Zhou C, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trialJ]. Lancet. 2021 Oct 9; 398(10308):1344-1357.
[3] Felip E, Altorki N, Zhou C, et al. Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial. Ann Oncol. 2023 Oct; 34(10):907-919.
[4] Cascone T, et al. Annals of Oncology, 2023, 34: S1295.
[5] Heymach J V, et al. New England Journal of Medicine, 2023, 389(18): 1672-1684.
[6] Wakelee H, et al. New England Journal of Medicine, 2023, 389(6): 491-503.
[7] Lu S, et al. JAMA, 2024, 331(3): 201-211.
[8] Yue D, et al. Annals of Oncology, 2023, 34: S1299.
[9] Forde P M, et al. New England Journal of Medicine, 2022, 386(21): 1973-1985.
[10] Jonathan Spicer,et al. Poster 8521.2023 ASCO
[11]2024 NCCN NSCLC Guideline
*As of writing: April 9, 2024* This article is only for the purpose of providing scientific information to medical professionals and does not represent the views of this platform