2022 CSCO Interpretation of Guidelines for the Diagnosis and Treatment of Biliary Malignant Tumors——Professor Zhou Jun's Interpretation of the Systematic Diagnosis and Treatment of Cholangiocarcinoma

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 BRAF^V600E 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.