*For medical professionals for reference
Looking for the advantages of immunotherapy to improve the survival benefits of BTC patients.
Balile vicious (BTC) is a malignant tumor with high degree of malignant degree, which has strong invasion, great treatment difficulty in treatmentThe characteristics.For early BTC patients, surgical resection is the only healing method.However, after the treatment of treatment, the recurrence rate of the disease is still high.For patients with late BTCs, the survival benefits brought about by chemotherapy and chemotherapy for the treatment of BTC first -line standards in the past 10 years are limited.
Until the announcement of Topaz-1 research results [1], BTC treatment officially entered the era of immunotherapy, and OS successfully exceeded 1 year.Subsequently, more research results of immunochemical combined chemotherapy were announced, and the research results of Keynote-966 [2] showed that Paborizumab combined with Geshabin and cisplatin can improve the survival benefits of BTC patients, further confirming that immunochemical combined chemotherapy brought aboutImprovement of survival benefits.Although these studies have made certain progress in the BTC field, those patients have not been found to benefit from immunotherapy and have relatively few data about genome characteristics on the efficacy.Therefore, in -depth understanding of the molecular characteristics of patients with BTC will not only help determine the superior immunotherapy people, but also open a path for further research on new assisted therapy and auxiliary therapy.familyThe mutation type group analyzes the analysis results with the clinical ending.The study was included in a total of 138 patients with advanced BTCs. Among them, 51 patients were selected to use second -generation sequencing (NGS) Foundation ONE gene detection combination for genomic analysis, and then mutations -based oncate cluster analysis and survival analysis were performed.Patients in the group were injected at the 1st and 8th day of the 21 -day cycle. Gycisbine + Cisplatin was administered at a maximum of 8 cycles.On the first day of each cycle, patients with BTC patients were accepted by Diaopolipumab combined with chemotherapy.After the treatment of the 8 -cycle, 1 degree of anti -single drug treatment is given every 4 weeks of BTC patients until the disease is progressing or intolerance.
Research results
➤ cluster analysis results
Researchers first analyzed molecular analysis of patients in the group, and selected genome mutations that can be observed among more than 5%of patients for clustering analysis. These genome mutations involved 37 genes.Among the 37 genes with mutation frequency ≥5%, 30 were included in the carcinogenic pathway (MCP) list that existed in artificially screening, so it was included in the analysis of clustering.Researchers mainly divide patients into three clusters. The first cluster includes 13 patients (cluster 1), the second cluster includes 27 patients (cluster 2), and the third cluster includes 11Patients (cluster 3).The characteristics of the three different clusters are changes in genes of different pathways.Except for the baseline blood levels of CA19-9, three patients with different clustering classes have similar baseline characteristics.Because compared with patients with cluster 1 and cluster 2, there are fewer patients with higher CA19-9 levels in cluster 3.
By analyzing the number of mutant genes of three clustering class, the number of mutation genes of clustering 2 can be found that the number of mutation genes is the largest.15 analysis genes and 13 analysis genes.In terms of main features, clustering 1 is mainly manifested in mutation of genes related to chromatin modification pathways, and the mutation rate is 100%.The characteristics of clustering 2 are mutations in multiple pathways, of which DNA damage control (81%), chromatin modification (78%), RTK/RAS (63%), cyclical apoptosis (59%), TP53 (48%) And PI3K (30%) are the main.The main ways of mutation in cluster 3 are RTK/RAS (36%) and cyclical apoptosis (27%).
➤ Survival analysis results
Survival analysis based on the results of clustering analysis, and the results show:
In terms of PFS, the medium -bit PFS of the polyclass 2 is 8.88 months, and the median PFS of polyclass 1 and cluster 3 is 6.45 months and 6.25 months (P = 0.5605).Scholarship.
In terms of OS, there is no statistics between clustering 1, cluster 2 and cluster 3Learning differences.
Among the three clusters, clustering 1, cluster 2 and cluster 3 availableThe number of people in the relief rate analysis is 13, 24, and 10, respectively.In terms of objective relief rate (ORR), the ORR of clustering, clustering 2, and clustering 3 are 4/13 (31%), 12/24 (50%), and 0/10 (0%).Statistical significance (P = 0.0188).
In terms of disease control rate (DCR), clustering, cluster 2 and clustering3 DCRs are 8/13 (61.5%), 12/24 (50%), and 9/10 (90%) (p = 0.09).
In terms of bad events, the three clustering categories have no statistically significant significance.
Research conclusion
This researchFor the first time, a cluster analysis was performed on BTC patients with first -line therapy as a Patabrot Mippitive combined chemotherapy. The analysis highlighted three clusters with different molecules and genome characteristics.The results showed that there were significant differences in the relief rate of the three groups of patients. Among them, the ORR of the cluster 2 was the highest, reaching 50%, and theRR of the cluster 3 was the lowest at 0%.
Analysis and Discussion
Topaz-1 Studies show that compared with patients with metastasis, local late BTCPatients can benefit more from immunochemical chemotherapy.In addition, SWOG 1815 Studies [4] confirmed that Jesitabin+cisplatin+white protein paclitaxel triminal pharmaceutical chemotherapy can bring survival benefits to patients with local advanced stages, and cannot bring survival benefits to patients with metastatic BTC.It can be seen that in the treatment of late tumors, there are certain differences in the relief rate of different genetic types.
Back to the research discussed in this article, no patients in the cluster 3 have achieved objective relief.Instead, the BTC patients in Polytes 2 reached 50%.Therefore, there may be immune superiority in clustering 2, but this speculation requires greater samples to support.Genetic detection shows that patients with clustering 2 are rich in genetic mutations such as BRCA2 and ATM. These gene mutations produce BRCANESS phenotyps.In a retrospective study [5], compared with BRCANESS wild -type patients, after BRCANESS mutant BTC patients received the first -line treatment of chemotherapy, the PFS improved significantly, and OS was also improved.In addition, more and more evidence has proved that the DNA damage repair system may change the stability of the genome, thereby promoting local antigen release and enhancing the immunogenicity of tumors.Therefore, patients with Brcness not only have a good response to chemotherapy, but also have a good response to immunotherapy.The same is true in TOPER research. Patients with mutations in BRCA1/2 mutations in Cisplatin+Gascotabine+Daguari Mipida have higher ORR compared to wild patients.In the future, the samples of related research should be expanded, exploring the characteristics of immunoagers in patients with BTC, and bringing more accurate and individualized treatment plans to BTC patients.
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References:
[1] .oh dy, et al. A Phase 3 randomized, double-black, placebo-controlled study of durvalumab in operation E Plus Cisplatin (Gemcis) inPatients (PTS) With Advanced Bilily Tract Cancer (BTC): Topaz-1. Nejm Evid. 2022; 1 (8).
[2]. Kelley RK, et al. PEMBROLIZUMABIn Combination with Gemcitabine and Cisplatin Compared with Gemcitabine and Cisplatin Alone For Patients with Advanced Cancer (Keynote-966): A RANDOMISE D, double-black, contina-controlled, phase 3 trial. Lancet. 2023 jun 3; 401 (10391): 1853-1865.
[3] .rimini m, et al. Different Genomic clusters IMPACT On Responses in Advanced Cancet with Cisplatin Gemcitabine Plus Durvalumab. Target Oncol. 2024Feb 12.
[4] .rachna T, et al.SWOG 1815: A Phase III RANDONDIZED TRIAL of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versusus Ine and cisplatin in Newly Diagnosed,Advanced Biliary Tract Cancers.2023 ASCO GI Abstract LBA490.
[5] .golan T, et al. IC Pancreatic Cance. N English J Med. 2019; 381 (4): 317–27
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