Preface
The annual meeting of the American Society of Clinical Oncology (ASCO), an annual oncology academic event, has recently come to an end. During this year's ASCO Annual Meeting, many blockbuster studies in the field of lung cancer that have led to clinical change were published. As one of the most cutting-edge and advanced concepts in the current diagnosis and treatment of lung cancer, the field of immunotherapy has also ushered in the publication of a number of blockbuster perioperative research data, adding strong evidence to perioperative immunotherapy. To this end, Yimaitong invited Professor Wu Nan from Peking University Cancer Hospital to sort out and analyze the research progress related to perioperative immunotherapy for NSCLC at the 2024 ASCO Congress, and discuss how to choose the current immunotherapy model.
Expert Profile
Professor Wu Nan
- Doctor of Medicine, Chief Physician, Professor, Doctoral Supervisor
- Vice President of Peking University Cancer Hospital and Deputy Director of Thoracic Cancer Center
- Expert who enjoys the special government allowance of the State Council
- Past Chair of the Membership Committee of the International Association for the Study of Lung Cancer (IASLC).
- Member of the Oncology Branch of the Chinese Medical Association
- Member of the Thoracoscopy Group of the Chinese Thoracic and Cardiovascular Surgery Branch
- He is a member of the Standing Committee of the Multidisciplinary Diagnosis and Treatment Committee of the Chinese Medical Doctor Association and a member of the Thoracic Surgery Branch
- Member of the Non-Small Cell Lung Cancer Expert Committee of the Chinese Society of Clinical Oncology (CSCO).
- Vice Chairman of the Tumor Chemotherapy Professional Committee of the Chinese Medical Education Association
- Member of the Standing Committee of the Geriatric Oncology Branch of the Chinese Society of Gerontology and Geriatrics
- Vice Chairman of the Oncology Branch of Beijing Medical Association, Member of the Standing Committee of the Thoracic Surgery Branch
Tumor shrinkage and downstage, delay recurrence two-pronged,
Perioperative immunotherapy helps N2 patients achieve long-term survival
For patients with early-stage and partially locally advanced non-small cell lung cancer (NSCLC), surgical treatment is the main treatment to help improve survival and achieve clinical cure. However, the efficacy and indications of surgical treatment have been controversial for patients with highly heterogeneous stage III NSCLC, especially those with N2 lymph node involvement. These patients are often accompanied by multiple micrometastases, especially in the case of multi-station N2 metastases, which are difficult to achieve complete resection by surgery alone, and there is a very high risk of postoperative recurrence and metastasis, which seriously affects the prognosis of patients.
In response to this challenge, perioperative immunotherapy has shown its therapeutic potential. The addition of immunotherapy helps to reduce and eliminate micrometastases while shrinking the primary lesion, reducing tumor stage, increasing surgical resection rates, and reducing the risk of postoperative recurrence in patients1. Perioperative immunotherapy provides an effective treatment strategy for stage III NSCLC patients, who are highly heterogeneous and have a high disease burden.
At this year's ASCO Annual Meeting, the AEGEAN and CheckMate 77T studies in the perioperative immunotherapy area of NSCLC updated exploratory results in their N2 subgroup populations, respectively, and the results presented by the AEGEAN study showed that the event-free survival (EFS) benefit (HR = 0.63) of perioperative immunotherapy in the N2 subgroup was similar to that of the overall mITT population, regardless of whether the patient had single-station or multi-station N2 lymph node metastases.
In the CheckMate 77T study, which analyzed efficacy in patients with stage III N2 and non-N2 NSCLC, patients with a higher risk of N2, multi-station micrometastases were more likely to benefit from perioperative immunotherapy (N2, EFS HR=0.46 vs. non-N2, EFS HR=0.60; single-station N2, EFS HR= 0.49 vs. multi-station N2, EFS HR= 0.43) (see Figure 1). In addition, the study also found that patients with non-pCR benefited more from perioperative immunotherapy than perioperative chemotherapy, both N2 and non-N2, and that the benefit of EFS in the N2 population was greater (HR=0.48 vs. HR=0.86)3,4 (see Figure 2), suggesting that the role of postoperative adjuvant immunotherapy is crucial in non-pCR patients with residual disease postoperatively, especially in patients with stage N2 disease.
Figure 1. EFS outcomes in N2 versus non-N2 patients in the CheckMate 77T study3,4
Figure 2. EFS outcomes in patients with no pCR in N2 versus non-N2 in the CheckMate 77T study3
The N2 subgroup data from the two studies together express the idea that perioperative immunotherapy can significantly improve EFS and pathologic complete response (pCR) in patients in the N2 subgroup without increasing the difficulty of surgery, further supporting that perioperative immunotherapy is an effective treatment strategy for patients with resectable NSCLC, especially those with stage III N2 who have a poor prognosis. This can also be supported in the NEOTORCH study, where the highest proportion of N2 patients was included, 4-8.
Higher N2 ratio, higher benefits,
The NEOTORCH study sets a new benchmark for perioperative immunotherapy
NEOTORCH Study 8 is a randomized, double-blind, placebo-controlled, Phase III clinical study to evaluate the efficacy and safety of toripalimab plus platinum-doublet chemotherapy versus placebo plus platinum-doublet chemotherapy in patients with stage II-III resectable NSCLC. Unlike the previously mentioned CheckMate 77T and AEGEAN studies, the NEOTORCH study enrolled predominantly Phase III patients and included a higher proportion of patients with stage N2 disease (70%) (Table 1).
Table 1 The proportion of baseline N2 patients enrolled in similar studies of perioperative immunotherapy4-8
*: Experimental group/control group
**: Whole population
: This is a non-head-to-head study, not a direct comparison, and is intended for medical professionals only
The results of the NEOTORCH study showed that 8-toripalimab plus chemotherapy significantly prolonged EFS in patients with stage III NSCLC compared with perioperative chemotherapy alone (NE vs. 15.5 months, P<0.0001), while the EFS HR value reached an unprecedented 0.40 (95%CI: 0.271-0.572), which means that the risk of postoperative recurrence was reduced by up to 60%, demonstrating the importance of perioperative immune intervention. Due to the inclusion of a high proportion of the N2 population in the study, the results of the study also reflect the strong benefit of perioperative treatment of toripalimab for patients with stage N2 NSCLC.
This outstanding result is largely due to the innovative "3+1+13" regimen in the NEOTORCH study, i.e., 3 cycles of toripalimab plus neoadjuvant chemotherapy + 1 cycle of consolidation chemotherapy + 13 cycles of adjuvant toripalimab. According to the Expert Consensus on Neoadjuvant Immunotherapy for Non-Small Cell Lung Cancer,1 the cycle of neoadjuvant immunotherapy is very important because short-term neoadjuvant immunotherapy may not be sufficient to make immunotherapy effective, while long-term treatment may lead to tumor progression and loss of surgical window for patients. The NEOTORCH study chose a relatively shorter 3-cycle preoperative neoadjuvant therapy, which can effectively prevent patients from missing the opportunity to undergo surgery due to disease progression or adverse reactions compared with the common 4-cycle neoadjuvant therapy. In the NEOTORCH study, only 5.5% of patients in the toripalimab group had surgery cancelled due to disease progression or inability to tolerate adverse effects8. The innovative one-cycle consolidation chemotherapy combined with immunotherapy mechanistically helps to eliminate tumor cells and micrometastases that may be shed during surgery, and at the same time helps to ensure that the multidisciplinary team of medical and surgical departments pays attention to the patient, ultimately casting a strong benefit of this treatment option8.
At your fingertips, toripalimab has created a new era of "international quality, national price" immunity
At the end of 2023, toripalimab was officially approved as an indication for the perioperative treatment of patients with stage III resectable NSCLC9, and it is also the only* approved indication for the perioperative treatment of stage III NSCLC in China#, and is expected to be included in the national medical insurance catalogue next year, with excellent economy and accessibility in China. It is for this reason that toripalimab has also become the first and only* Level I recommendation for the perioperative treatment of stage III resectable NSCLC in the 2024 CSCO Guidelines for the Diagnosis and Treatment of NSCLC10 (Figure 3).
Figure 3. CSCO guidelines for the care of NSCLC recommend the treatment of stage III operable patients10
As a PD-1 monoclonal antibody independently developed by mainland China, its high quality has also obtained international certification: in October 2023, toripalimab was approved for marketing by the US FDA, becoming the first original PD-1 monoclonal antibody drug developed in mainland China to go overseas in the United States. At present, the first-line treatment and other indications for advanced NSCLC that have been approved in China have been included in the National Medical Insurance Catalogue11, which has greatly lowered the threshold for immunotherapy for domestic patients. THE SUCCESS OF THE EXTENTORCH STUDY HAS ALSO LED TO THE RECENT APPROVAL OF THE INDICATIONS FOR THE FIRST-LINE TREATMENT OF EXTENSIVE-STAGE SMALL CELL LUNG CANCER (ES-SCLC)12, ENABLING SMALL CELL LUNG CANCER PATIENTS TO ENJOY "INTERNATIONAL QUALITY" IMMUNOTHERAPY AT A "NATIONAL PRICE". It is believed that with the continuous breakthrough progress in immunotherapy, toripalimab will be able to take the lead in the new wave of lung cancer diagnosis and treatment reform and benefit the majority of lung cancer patients in China.
*: As of June 25, 2024
#: Refers specifically to the "sandwich cake" perioperative treatment mode of preoperative neoadjuvant therapy + postoperative adjuvant therapy
Bibliography:
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2. Provencio M, Awad M M, Spicer J, et al. Clinical outcomes with perioperative nivolumab (NIVO) by nodal status among patients (pts) with stage III resectable NSCLC: Results from the phase 3 CheckMate 77T study[J]. Journal of clinical oncology, 2024, 42 (suppl 17): LBA8007.
3. Heymach J, Reck M, Mitsudomi T, et al. Outcomes with perioperative durvalumab (D) in pts with resectable NSCLC and baseline N2 lymph node involvement (N2 R-NSCLC): An exploratory subgroup analysis of AEGEAN[J]. Journal of clinical oncology, 2024, 42 (suppl 17):
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8. Lu S, Zhang W, Wu L, et al. Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non–Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial[J]. JAMA, 2024, 331(3): 201-211.
9. National Medical Products Administration. 2024-01-02 Drug Approval Certificate Delivery Information Release[EB/OL]. 2024[2024-6-21]. https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20240102151646109.html.
10. Chinese Society of Clinical Oncology (CSCO) guidelines for the diagnosis and treatment of non-small cell lung cancer[M]. April 2024, 1st edition. People's Medical Publishing House, 2024.
11. National Health Security Administration. National Basic Medical Insurance, Work-related Injury Insurance and Maternity Insurance Drug Catalogue (2023)[EB/OL]. 2020[2024-6-14]. http://www.nhsa.gov.cn/art/2023/12/13/art_53_11674.html
12. National Medical Products Administration. 2024-06-12 Drug Approval Certificate Delivery Information[EB/OL]. 2024[2024-6-21]. https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20240612124002121.html
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