
==== Front
Aging Med (Milton)
Aging Med (Milton)
10.1002/(ISSN)2475-0360
AGM2
Aging Medicine
2475-0360
John Wiley and Sons Inc. Hoboken

10.1002/agm2.12356
AGM212356
AGM-2024-0082.R3
Commentary
Commentary
The efficacy of neoadjuvant immunotherapy combined with chemotherapy in elderly patients with gastric cancer: A subgroup analysis of the NEOSUMMIT‐01 study
An et al.
An Nan https://orcid.org/0009-0001-6240-4719
1
Nie Run‐cong 1
Wang Feng 2 3
Yuan Shu‐qiang 1 yuanshq@sysucc.org.cn

1 Department of Gastric Surgery Sun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou China
2 Department of Medical Oncology Sun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat‐sen University Guangzhou China
3 Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer Chinese Academy of Medical Sciences Guangzhou China
* Correspondence
Shu‐qiang Yuan, Department of Gastric Surgery, Sun Yat‐sen University Cancer, Center, State Key Laboratory of Oncology in South China, Collaborative Innovation, Center for Cancer Medicine, Guangzhou 510060, China.
Email: yuanshq@sysucc.org.cn

18 8 2024
8 2024
7 4 10.1002/agm2.v7.4 453455
17 4 2024
04 8 2024
© 2024 The Author(s). Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

Based on a subanalysis of the NEOSUMMIT‐01 study, it was revealed that perioperative immune checkpoint blockade (ICB) combined with chemotherapy has therapeutic effects in elderly patients with locally advanced gastric cancer, providing a new strategy for the treatment of elderly gastric cancer patients.

gastric cancer
immunotherapy
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cover-dateAugust 2024
details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.4.8 mode:remove_FC converted:03.09.2024
An N , Nie R‐c , Wang F , Yuan S‐q . The efficacy of neoadjuvant immunotherapy combined with chemotherapy in elderly patients with gastric cancer: A subgroup analysis of the NEOSUMMIT‐01 study. Aging Med. 2024;7 :453‐455. doi:10.1002/agm2.12356
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pmcGastric cancer is globally recognized as one of the most prevalent and aggressive cancer types, ranking fifth in incidence and fourth in mortality among all cancer types. 1 It is principally treated by radical surgical resection for early‐stage and locally advanced cases, aiming to eradicate the disease and enhance survival. However, patients with locally advanced gastric cancer are at significant risk of recurrence after surgery, often linked to micrometastases. 2 Perioperative or adjuvant chemotherapy has been proven to improve clinical outcomes compared to surgery alone. The MAGIC trial demonstrated a breakthrough discovery, showing that administering epirubicin, cisplatin, and fluorouracil (ECF) before surgery increased survival. 3 The multicenter phase 3 trial RESOLVE examined the efficacy of S‐1 and oxaliplatin (SOX) before surgery in patients with locally advanced gastric cancer compared to capecitabine combined with oxaliplatin. The findings revealed that perioperative SOX substantially prolonged disease‐free survival, with 3‐year survival rates reaching 59%, compared to 51% for adjuvant capecitabine and oxaliplatin. 4 In recent years, immune checkpoint blockade (ICB) therapy has shown promise in the field of gastric cancer. The combination of chemotherapy and ICB markedly enhances overall survival (OS) and progression‐free survival (PFS) in participants with metastatic gastric carcinoma compared to chemotherapy alone, as confirmed by the Checkmate 649 and Orient‐16 trials. This underscores the pivotal role of combining chemotherapy and ICB in the management of advanced gastric carcinoma. 5 Despite these advancements, a study comparing perioperative ICB with chemotherapy versus chemotherapy alone is urgently needed.

The NEOSUMMIT‐01 was a randomized, open‐label Phase 2 trial conducted by our team, involving patients diagnosed with gastric cancer or gastroesophageal junction cancer at clinical stage cT3‐4aN + M0. 6 A total of 108 participants were randomly allocated in equal proportions to either the chemotherapy group or the combination therapy group. The former received three cycles of XELOX/SOX treatment before surgery and five cycles postoperatively, while the latter received ICB (toripalimab) alongside XELOX/SOX, followed by a monotherapy period lasting at least 6 months. Researchers found that the combination therapy group attained a higher percentage of pathological complete responses or near‐complete responses (tumor regression grade (TRG) 0/1) than the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%–58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%–33.5%)). Furthermore, the incidence of fatalities as well as adverse events of grades 3–4 related to treatment (1.9% vs 0% and 35.2% vs 29.6%) demonstrated no notable differences between the chemotherapy group and the combination therapy group.

A review of the authoritative cancer statistics from the Surveillance, Epidemiology, and End Results (SEER) database in the United States reveals that over 60% of gastric cancer patients are elderly individuals aged 65 and above. 7 With the acceleration of the aging process, the proportion of elderly gastric cancer patients is expected to increase further. Due to the presence of multiple comorbidities, poor nutritional status, and compromised immune function among elderly patients, they are at heightened susceptibility to postoperative complications and negative outcomes. This underscores the need for more meticulous consideration in selecting clinical treatment strategies. To explore the contribution of ICB therapy during perioperative care in the elderly, a sensitivity analysis was conducted on patients aged 60 and above in NEOSUMMIT‐01. Based on the baseline data, there was no noticeable difference between the two groups (Table 1). Compared with chemotherapy patients, those in the combination group had a higher percentage of TRG 0/1 (46.1% [95% CI: 27%–65.3%] versus 20% [95% CI: 5.7%–34.3%], p = 0.045) (Figure 1).

TABLE 1 Baseline characteristics of the ITT population.

Characteristics	Toripalimab + chemotherapy (n = 26)	Chemotherapy (n = 30)	
Age, years			
Median (IQR)	67 (60–74)	67 (60–74)	
>60	100%	100%	
Sex			
Male	19 (73.1%)	22 (73.3%)	
Female	7 (26.9%)	8 (26.7%)	
ECOG performance status			
0	15 (57.7%)	18 (60%)	
1	11 (42.3%)	12 (40%)	
Tumor location			
Gastric	12 (46.2%)	16 (53.3%)	
Gastroesophageal junction	14 (53.8%)	14 (46.7%)	
Clinical tumor stage			
cT3	10 (38.5%)	10 (33.3%)	
cT4a	16 (61.5%)	20 (66.6%)	
Clinical node stage			
cN1	9 (34.6%)	13 (43.3%)	
cN2	13 (50%)	15 (50%)	
cN3	4 (15.4%)	2 (6.7%)	
Lauren's classification			
Diffuse	5 (19.2%)	10 (33.3%)	
Intestinal/Mixed	21 (80.8%)	20 (66.6%)	
Signet‐ring cell composition			
No	24 (92.3%)	23 (76.7%)	
Yes	2 (7.7%)	7 (23.3%)	
Chemotherapy regimen			
SOX	15 (57.7%)	13 (43.3%)	
XELOX	11 (42.3%)	17 (56.7%)	
PD‐L1 combined positive score			
<5	15 (57.7%)	22 (73.3%)	
≥5	6 (23.1%)	2 (6.7%)	
Could not be evaluated	5 (19.2%)	6 (20%)	
Abbreviations: ECOG, EasternCooperative Oncology Group; SOX, S‐1 and oxaliplatin; XELOX, xeloda and oxaliplatin.

FIGURE 1 Subgroup analysis of the elderly population (≥65 years old) in the NEOSUMMIT‐01 study.

In summary, the analysis from the NEOSUMMIT‐01 study has confirmed that incorporating ICB therapy alongside chemotherapy during the perioperative period can significantly enhance the pathological response rate in elderly patients diagnosed with locally advanced gastric carcinoma. This discovery provides novel evidence regarding treatment modalities for this elderly demographic afflicted with gastric cancer. However, it is important to note that this study is based on a subgroup analysis of the NEOSUMMIT‐01 clinical trial, which had strict inclusion and exclusion criteria. Patients over the age of 75 and those with poor baseline conditions were excluded. 6 Therefore, the potential benefits of neoadjuvant immunotherapy combined with chemotherapy for patients over 75 remain uncertain and require further clinical data for confirmation. Additionally, the high incidence of adverse reactions and other drug safety issues in elderly patients necessitates further validation. The administration of medication in elderly gastric cancer patients is still a critical issue in clinical practice. We anticipate more targeted clinical trials focusing on elderly populations in the future to provide additional treatment options for elderly gastric cancer patients.

AUTHOR CONTRIBUTIONS

Nan An was responsible for conceptualization, writing the original draft, and preparing figures and tables. Run‐cong Nie contributed to writing, review, and editing. Feng Wang and Shu‐qiang Yuan were involved in conceptualization, supervision, and review and editing.

FUNDING INFORMATION

This research was supported by the National Natural Science Foundation of China (Grant No. 81302144) and the Guangdong Esophageal Cancer Institute Science and Technology Program (M02210).

CONFLICT OF INTEREST STATEMENT

The authors declare no relevant financial or non‐financial interests to disclose.

ETHICS STATEMENT

This study is based on a subgroup analysis of previously conducted clinical trials. The clinical trial data have been openly published, and the associated ethical information is accessible at the publication location.

ACKNOWLEDGMENTS

The authors express their gratitude to everyone who contributed to this work.
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