-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Patients with biliary malignancy (BTC) have a very poor
prognosis.
In recent years, its morbidity and mortality have continued to rise
.
BTC patients mainly include gallbladder cancer (GBC) and cholangiocarcinoma (CCA), which can be roughly divided into two subtypes
: intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC).
It is well known that clarifying the unique molecular pathogenesis of ICC and ECC can help with early diagnosis and precision treatment, thereby improving patient outcomes¹
.
In order to standardize the precision diagnosis and treatment of CCA, the Guidelines Working Committee of the Chinese Society of Clinical Oncology compiled the "2022 Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Biliary Malignant Tumors" (hereinafter referred to as the "Guidelines"), aiming to transmit the latest research progress of BTC and provide the latest authoritative evidence support
for the diagnosis and treatment of BTC patients.
Expert profiles
Professor Zhou Jun
Associate Chief Physician, Department of Gastroenterology, Peking University Cancer Hospital, Ph.
D.
in OncologyMember of CSPAC of Pancreatic Cancer Professional Committee of Chinese Anti-Cancer Association
Secretary of the CSCO Expert Committee on Gastrointestinal Stromal Tumors
Secretary of the Gastrointestinal Cancer Branch of the Chinese Geriatric Cancer Association
Secretary of the Chinese Gastrointestinal Cancer Clinical Research Collaboration Group
Member of the secretary group of the "Colorectal Cancer Diagnosis and Treatment Standard" of the Ministry of Health
In the past ten years, he has focused on the standardized and individualized treatment of digestive system medical oncology
Screening and diagnosis of cholangiocarcinoma
Patients with BTC are rare, accounting for about 3%
of all digestive tumors.
The vast majority of BTC is adenocarcinoma, highly aggressive, mostly advanced at the time of discovery, with a very poor prognosis, and a 5-year survival rate of less than 5%.
At present, the global incidence of BTC is on the rise, with Asian countries being the most common
.
Guidelines recommend: pay attention to the collection of clinical data, and emphasize auxiliary examinations such as imaging and pathological histology
Interpretation 1: Histology and/or cytology is the gold standard for diagnosing BTC
Ultrasound, serum CEA and CA19-9, multi-stage enhanced CT or MRI of the abdomen and pelvis, chest CT, magnetic resonance pancreatobiliary imaging (MRCP), ERCP, exfoliative cell examination, etc.
play an important role in the diagnosis of CCA, the formulation of treatment plans and the evaluation of efficacy, and pathological histological and/or cytology are the gold standard
for the diagnosis of BTC.
According to the stratification of patients, the guidelines give targeted diagnosis and efficacy evaluation recommendations, in order to provide guidance and assistance to clinicians²
.
Table 1 Screening and diagnosis of CCA
Interpretation 2: The mass type ICC recommends adding FGFR2 break probe FISH detection and IDH1/2 generation sequencing
Immunohistochemistry is an indispensable test in the pathological differential diagnosis of cholangiocarcinoma, such as biliary adenocarcinoma (CK7, CK19 are usually positive, while CK20 is usually negative), fine cholangiocarcinoma (CD56+), squamous cell carcinoma (P40, P63+), neuroendocrine carcinoma (Syn, CgA+).
In addition, immunohistochemistry can detect some targeted therapy or immunotherapy targets, including c-MET, EGFR, Her2, MLH1, MSH2, MSH6, PMS2, etc
.
MLH1, MSH2, MSH6, PMS2 protein expression detection can determine the MMR status, and can also do MSI and other molecular detection
.
For ICC, especially mass ICC, it is recommended to add FGFR2 break probe FISH detection and IDH1/2 generation sequencing, or second-generation sequencing detection
.
Patients who have not been tested by next-generation sequencing can also be tested for c-MET, Her2, NTRK1-3 and first-generation sequencing: BRCA1/2, BRAF, etc.
²
.
Table 2 Pathological diagnosis of BTC
First-line treatment for advanced biliary malignancies
Guidelines recommend: first-line patients with advanced biliary malignancy should be treated systematically
For patients who can tolerate intense chemotherapy, gemcitabine + cisplatin + duvalumab, gemcitabine + tigio/cisplatin, capecitabine + oxaliplatin are the first-line treatment options for advanced BTC
.
Other first-line regimens include albumin paclitaxel-based chemotherapy, 5-fluorouracil (5-FU) + platinum
.
In this year's guidelines, based on the results of TOPAZ-1 studies, gemcitabine + cisplatin + dupaliumab regimen was added as a first-line regimen
.
It is recommended that all BTC patients who meet the conditions for precision medicine participate in clinical studies, including but not limited to FGFR2 fusion mutations, IDH1/2 mutations, POLE/POLD mutations, BRCA mutations/BAP mutations/ATM mutations, BRAF mutations, etc.
²
.
Table 3 First-line treatment of advanced BTC
Interpretation: Add gemcitabine + cisplatin + durvalumab regimen and include it in the first-line regimen (class 1A evidence, level I recommendation)
The TOPAZ-1 study showed that durvalumab plus gemcitabine plus cisplatin increased overall survival (OS) from 11.
5 months to 12.
8 months and progression-free survival (PFS) from 5.
7 to 7.
2 months
in patients with advanced BTC.
Second-line treatment of advanced biliary malignancies
Guidelines recommend: For second-line patients with advanced biliary malignancies, give precise stratified therapy and actively try targeted therapy
Oxaliplatin + 5-FU (mFOLFOX) is used as the standard of second line therapy for patients with ECOG PS≤1
.
Other second-line regimens include regorafenib, pembrolizumab (MSI-H/dMMR tumors only), dabrafenib plus trametinib for BRAF V600E mutant tumors, and lvosidenib for IDH1-mutant
tumors.
In this year's guidelines, based on the results of FIGHT202 studies, new Pemigatinib was added for the treatment of patients with FGFR2 fusion/rearrangement tumors (level II recommendation); Based on the MyPathway study, Pertuzumab + trastuzumab was added for the treatment of patients with HER2-positive tumors (class II recommendation)²
.
Table 4 Second-line treatment of advanced BTC
Interpretation 1: Evonebub is included in the second-line treatment regimen for advanced BTC with IDH1 mutation (Class 1A evidence, level II recommendation)
The ClarIDHy study is a global multicenter phase III clinical study to evaluate the efficacy and safety
of ivosidenib compared with placebo in the treatment of patients with unresectable or metastatic IDH1-mutant cholangiocarcinoma.
Patients enrolled in the study with advanced IDH1-mutant cholangiocarcinoma were randomized 2:1 to receive the IDH1 inhibitor ivosnib (500 mg PO QD) or placebo
.
As of May 31, 2020, a total of 187 patients were enrolled in the study, who were randomized to ivonyb (n=126) or placebo (n=61); The results showed that the median PFS was 2.
7 months vs 1.
4 months, OS 10.
3 months versus 5.
1 months, respectively, and the longest duration of treatment was 34.
4 months in the ivounib group versus 6.
9 months in placebo, and the median duration of treatment was 2.
8 months versus 1.
6 months, respectively, all of which were statistically significant
.
Figure 1 ClarIDHy research OS results
Figure 2 ClarIDHy study PFS results
The ivoneb group showed good tolerability compared to placebo, and the adverse event during ≥ grade 3 treatment was ascites in both groups, and no treatment-related deaths
were observed.
The degree of decline in physical function in the ivozenib group was significantly lower than that in the placebo group, which proved that ivosidenib brought better survival and safety and controllability to patients with advanced IDH1-mutant cholangiocarcinoma³⁻⁴
.
Interpretation 2: Regorafenib is included in the second-line treatment regimen for BTC (Class 2B evidence, level II recommendation)
The REACHIN study enrolled patients with advanced cholangiocarcinoma following the progression of first-line gemcitabine plus platinum-based chemotherapy and randomized to regorafenib or placebo
.
The results showed that the median PFS of 3.
0 months versus 1.
5 months in the regorafenib group and the placebo group was statistically significant, but there was no significant difference in OS between the two groups, so it was recommended
as level II.
Interpretation 3: Dabrafenib plus trametinib is included in the second-line treatment regimen for advanced BTC with BR AF V600E mutation (class 2A evidence, level II recommendation)
A phase II single-arm, multicenter study enrolled patients with advanced or recurrent biliary tract cancer with BRAFV600E mutations who failed systemic therapy, all receiving dabrafenib and trametinib until disease progression or treatment intolerance
.
Of the 43 patients enrolled, 22 had remission and an ORR of 51%.
Interpretation 4: Newly added Pemigatinib as a second-line treatment regimen for advanced BTC with FGFR2 fusion/rearrangement (Class 2A evidence, level II recommendation)
There are 13%~20% of patients with FGFR2 fusion mutations in intrahepatic cholangiocarcinoma, and Pemigatinib/Infigratinb/Futibatinib are three representative drugs
targeting FGFR2 fusion mutations.
Interpretation 5: Pertuzumab + trastuzumab is added to the HER2-positive second-line treatment regimen for advanced BTC (class 2A evidence, level II recommendation)
The MyPathway study enrolled 39 patients with HER2-positive biliary tumors, and with pertuzumab + trastuzumab, 9 of the 39 patients were in remission
。 The ORR was 23%, and the HERB study was a phase II, single-arm, multicenter study of HER2-positive biliary tumors that failed gemcitabine treatment, using Trastuzumab deruxtecan (T-DXd, DS-8201), 8 of the 22 patients enrolled had remission, and the ORR was 36.
4%, but 2 of them died
due to severe lung injury.
Deliver CSCO's strongest voice, Chinese wisdom, and change Chinese practice
In recent years, many advances have been made in basic and clinical research in the field of cholangiocarcinoma, and the improvement of systematic anti-tumor programs such as targeted therapy and immunotherapy has made patients with cholangiocarcinoma have more treatment options
.
With the progress of clinical research in China, the update of guidelines is increasingly based on Chinese research and the disease characteristics of Chinese patients, and CSCO guidelines truly reflect the power
of China in international clinical progress.
It is hoped that with the advent of new drugs and the development of clinical trials, higher quality evidence-based medical evidence can be provided, and jointly help Chinese cholangiocarcinoma patients get a better tomorrow!
References:
1.
WANG Yingzhen, ZENG Yeting, WANG Xinrui, et al.
Molecular alterations and targeted therapy for intrahepatic and extrahepatic cholangiocarcinoma[J].
Journal of Clinical and Experimental Pathology, 2022(038-001).2.
Guidelines Working Committee of Chinese Society of Clinical Oncology.
Guidelines for the diagnosis and treatment of biliary malignant tumors of the Chinese Society of Clinical Oncology (CSCO)(2021)[M].
People's Medical Publishing House.3.
Andrew X.
Zhu; Teresa Macarulla, MD; Milind M.
Javle, MD,etal,Final Overall Survival Efficacy Results of Ivosidenib for Patients With Advanced Cholangiocarcinoma With IDH1, JAMA Oncology.4.
Prof Ghassan K Abou-Alfa,Teresa Macarulla,Prof Milind M Javle,etal,Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study.
Lancet Oncol.
2020 June ; 21(6): 796–807.
Edited by Candy
Reviewer: Big Circle
Typesetting: Wanderer
Execution: Traveler
This platform is designed to deliver more medical information
to healthcare professionals.
The content published on this platform cannot replace professional medical guidance in any way, nor should it be regarded as diagnosis and treatment advice
.
If such information is used for purposes other than understanding medical information, this platform does not assume relevant responsibilities
.
The content published by this platform does not mean that it agrees with its description and views
.
If copyright issues are involved, please contact us and we will deal with
it as soon as possible.
