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In August 2021, based on the results of CheckMate-649 research, nivolumab (trade name: Odivo ®) became the first PD-1 inhibitor approved in China for the first-line treatment of advanced gastric cancer in the whole population
。 In view of the breakthrough progress of gastric cancer immunotherapy, experts in various fields are invited to interpret the cutting-edge literature and research of gastric cancer immunotherapy to help improve the standardized application of immunotherapy in the clinical practice
of gastric cancer in China.
The eighth issue of "Stomach to Xianfeng" specially invited Professor Shi Min of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine to deeply analyze the effects of different PD-L1 detection antibodies on PD-L1 expression levels and invited him to share valuable clinical experience
.
Yimaitong: The PD-L1 detection antibodies corresponding to different types of immunotherapy drugs are different, please ask Professor Shi Min to talk about the impact of different PD-L1 detection antibodies on PD-L1 expression levels?
Professor Shi Min
Immune checkpoint inhibitors (ICIs) represented by PD-1/PD-L1 monoclonal antibodies have become the standard treatment for advanced gastric cancer, and with the approval of more and more ICIs, the corresponding PD-L1 detection antibodies have also been approved as auxiliary diagnostic drugs to guide the clinical selection of immunotherapy populations and predict the efficacy of immunotherapy1
.
However, there is still considerable uncertainty as
to whether the combined positive score (CPS) is consistent between different PD-L1-detected antibodies.
Therefore, NUH conducted a cross-sectional study to explore the interchangeability of Dako 22C3, Dako 28-8 and Ventana SP-142 antibodies in the PD-L1 immunohistochemistry assay for gastric cancer2
.
The study used multiplex immunohistochemistry/immunofluorescence techniques to score PD-L1 CPS, tumor cell positivity ratio score (TPS), and immune cell (IC) in 362 gastric cancer samples, which were obtained
by gastric cancer biopsy or surgical resection.
Studies have shown that when the cut-off values are CPS≥1, ≥5, and ≥10, the proportion of PD-L1 positive samples detected with 28-8 antibody is higher
than that of 22C3 antibody.
When CPS≥1, the positive proportion of PD-L1 was 70.
3% vs 49.
4% (p<0.
001); When CPS≥5, the positive proportion of PD-L1 was 29.
1% vs 13.
4% (p<0.
001); At CPS≥10, the proportion of PD-L1 positivity was 13.
7% vs 7.
0% (p=0.
004).
Figure 1: Proportion of PD-L1 positive detection with 28-8 and 22C3 antibody tests at CPS ≥1, ≥5 and ≥10
In addition, the mean CPS score (6.
39±14.
5) of 28-8 antibody detection was significantly higher than that of 22C3 antibody (3.
46±8.
98) and SP-142 antibody (4.
08±10.
3), while there was no significant difference between
the average CPS score of 22C3 and SP-142 antibody detection.
Figure 2: PD-L1 CPS scores for Dako 22C3, Dako 28–8 and SP-142
It is important to note that clinical trials using different PD-L1 detection antibodies have reported PD-L1 positive proportions that are also consistent
with the results of this study.
For example, the CheckMate-649 study using 28-8 antibodies reported 60% of CPS≥5 patients, twice as many as the KEYNOTE-061 study using 22C3 antibodies (31%)2,3
.
Therefore, the use of 22C3 antibodies instead of 28-8 antibodies may result in a significant reduction in the proportion of people benefiting nivolumab, especially those with
CPS≥5.
All in all, the findings do not support the interchangeability
of gastric cancer PD-L1 detection methods.
In the face of the complex status quo, effective clinicopathological communication is convenient for clinicians to standardize the application for PD-L1 immunohistochemical testing, pathologists to reasonably select PD-L1 detection antibodies and correctly report test results, so that more gastric cancer patients with higher PD-L1 expression levels can benefit from
PD-1 inhibitors.
Yimaitong: Could Professor Shi Min share your valuable experience in the application of PD-L1 detection and immunotherapy in clinical practice?
Professor Shi Min
In 2021, our hospital admitted a patient with advanced gastric cancer, and during laparoscopic exploration, multiple metastatic lesions were visible on the abdominal wall of the patient's right diaphragm, and perigastric lymph nodes were enlarged
.
Considering that radical resection was not possible, the operation
was terminated.
The pathological result of peritoneal metastases nodule biopsy is adenocarcinoma invasion/metastasis
.
Immunohistochemistry showed that PD-L1 CPS<1 (detection antibody was 22C3), HER2 gene detection (-), gene amplification<b13>.
Based on the CheckMate-649 study, nivolumab combined with chemotherapy may provide survival benefits to the first-line population of advanced gastric cancer, with a median overall survival (OS) of 13.
8 months4
.
Therefore, after giving the patient nivolumab combined with FLOT (docetaxel + oxaliplatin + 5-FU + leucovorin calcium), immunotherapy combined with chemotherapy for 6 courses, gastroscopy results showed no obvious lesions on the small curved side of the gastric body, and retreated
after treatment.
The results of repeat CT showed that the infiltrative lesions of gastric ulcers were significantly smaller than before, and the peritoneal multiple lymph nodes were narrowed compared with before, and partial remission (PR)
was considered.
Figure 3: Gastroscopy results before and after advanced first-line immunotherapy
Figure 4: CT results before and after advanced first-line immunotherapy
From the above cases, it can be seen that the patient used 22C3 antibody to detect PD-L1 CPS<1, that is, PD-L1 expression was negative, if the patient used the matching 28-8 antibody test, then PD-L1 expression may be negative or positive<b10>.
In practice, it is difficult to detect multiple antibodies in one specimen, which is often limited
by economics and specimens.
According to the 2022 CSCO guidelines for the diagnosis and treatment of gastric cancer, nivolumab combination chemotherapy has been recommended for the whole population with CPS≥5 and CPS<5 or PD-L1 detection5, and this patient has also benefited
from advanced first-line treatment with nivolumab combination chemotherapy.
Expert summary
1.
The consistency of PD-L1 antibody test results and interpretation needs more evidence, and even if PD-L1 test is negative, patients may still benefit
from immunotherapy.
2.
Nivolumab combined chemotherapy is suitable for the first-line whole population of
advanced gastric cancer.
References:
1.
National Center for Pathology Quality Control, Pathology Branch of Chinese Medical Association, Oncology Pathology Expert Committee of Chinese Society of Clinical Oncology, etc.
, Expert consensus on PD-L1 immunohistochemical detection of solid tumors (2021 edition).
Chinese Journal of Pathology,2021,50(7).
2.
Yeong J, Lum HYJ, Teo CB, et al.
Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy.
Gastric Cancer.
2022 Jul; 25(4):741-750.
3.
Janjigian YY, Shitara K, Moehler M, et al.
First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial.
Lancet.
2021; 398(10294):27–40.
4.
Shitara K, Jaffer AA, Moehler M, et al.
Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer.
Nature.
2022 Mar 23.
5.
Organized by the Guidelines Working Committee of the Chinese Society of Clinical Oncology.
Chinese Society of Clinical Oncology (CSCO) guidelines for the diagnosis and treatment of gastric cancer-2022[M].
Beijing:People's Medical Publishing House,2022.
]
Professor Shi Min
Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Executive Director of Ruijin Hospital Wuxi Branch
Doctor of Surgery, Deputy Chief Physician
Member of the Young Expert Committee of the Chinese Society of Clinical Oncology
Youth Committee Member of Integrated Oncology Branch of Chinese Anti-Cancer Association
Member of the New Seedling Committee of the Cancer Nutrition Committee of the Chinese Anti-Cancer Association
Member and Secretary of the Tumor Target Molecule Committee of Shanghai Medical Association
Youth member of Cancer Rehabilitation and Palliative Care Committee of Shanghai Anti-Cancer Association
Member of Shanghai Federation of Overseas Students
Shanghai European and American Students' Association
1506-CN-2202794
Edited by Dreams
Reviewed by Dreams
Typesetting: Youshi
Execution: Uni
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