Second-line Treatment In Biliary Tract Cancer Research Articles

A randomised phase II study of oxaliplatin/5-FU (mFOLFOX) versus irinotecan/5-FU (mFOLFIRI) chemotherapy in locally advanced or metastatic biliary tract cancer refractory to first-line gemcitabine/cisplatin chemotherapy

BackgroundIn locally advanced or metastatic biliary tract cancer (BTC), second-line chemotherapy is challenging after progression from first-line gemcitabine/cisplatin. This study evaluated whether irinotecan/5-fluorouracil (5-FU; mFOLFIRI) was superior to oxaliplatin/5-FU (mFOLFOX) as a second-line treatment in BTC. Patients and methodsPatients diagnosed with BTC with disease progression after prior gemcitabine/cisplatin were randomised (1:1) to either mFOLFOX (control arm) or mFOLFIRI (experimental arm). Randomisation was stratified by tumour location (intrahepatic versus extrahepatic versus gallbladder versus ampulla of Vater) and ECOG performance status (0, 1 versus 2). The primary endpoint was the overall survival (OS) rate at 6 months. ResultsIn total, 120 patients were enrolled and 118 patients were randomised (mFOLFOX n = 59, mFOLFIRI n = 59). The baseline characteristics were well balanced between the two arms. The tumour location was intrahepatic bile duct in 48 patients (40.7%), extrahepatic bile duct in 29 patients (24.6%), gallbladder in 35 patients (29.7%) and ampulla of Vater in 6 patients (5.1%). At a median follow-up duration of 25.8 months, the 6-month OS rate was 54.1% in mFOLFOX and 44.1% in mFOLFIRI (p = 0.677). The median OS was 6.3 months (95% CI, 4.4–8.2) in mFOLFOX and 5.7 months (95% CI, 4.7–6.7) in mFOLFIRI (p = 0.677). The median progression-free survival was 2.8 months (95% CI, 2.3–3.3) in mFOLFOX and 2.1 months (95% CI, 1.1–3.1) in mFOLFIRI (p = 0.974). Of the 101 evaluable patients, the objective response rate and disease control rate were 5.9% and 66.7% in mFOLFOX and 4.0% and 64.0% in mFOLFIRI (p = 0.663 and p = 0.778, respectively). Peripheral neuropathy (37.5% versus 5.2%) and thrombocytopenia (35.7% versus 15.5%) in mFOLFOX and vomiting (19.0% versus 1.8%) and cholangitis (10.3% versus 0.0%) in mFOLFIRI occurred more frequently. No chemotherapy-related death was reported. ConclusionIn the second-line treatment of BTC, mFOLFIRI was not superior to mFOLFOX. However, mFOLFIRI was tolerable and showed comparable efficacy to mFOLFOX. Adverse events were different between the two arms. ClinicalTrials.gov IdentifierNCT03464968

A randomized phase II study of oxaliplatin/5-FU (mFOLFOX) versus irinotecan/5-FU (mFOLFIRI) chemotherapy in locally advanced or metastatic biliary tract cancer refractory to first-line gemcitabine/cisplatin chemotherapy.

4603 Background: In locally advanced or metastatic biliary tract cancer (BTC), second-line chemotherapy is challenging after progression from first-line gemcitabine/cisplatin, although mFOLFOX has been proven to be superior to active symptom control in ABC-06 trial. Irinotecan is an active drug in other gastrointestinal cancers. This study evaluated whether mFOLFIRI was superior to mFOLFOX in second-line treatment of BTC. Methods: Patients diagnosed with BTC with disease progression after prior gemcitabine/cisplatin were randomized (1:1) to either mFOLFOX (oxaliplatin 100mg/m2 over 2 hours, leucovorin 100mg/m2 over 2 hours, 5-fluorouracil 2400mg/m2 over 46 hours, every 2 weeks) or mFOLFIRI (irinotecan 150mg/m2 over 2 hours, leucovorin 100mg/m2 over 2 hours, 5-fluorouracil 2400mg/m2 over 46 hours). Randomization was stratified by tumor location (intrahepatic vs extrahepatic vs gallbladder vs ampulla of vater) and ECOG performance status (0, 1 vs 2). Primary end-point was overall survival (OS) rate at 6 months. Results: In total, 120 patients were enrolled and 114 patients were treated (mFOLFOX:57, mFOLFIRI:57). Median age was 63 years old. Most patients had ECOG 0/1 (89.5%). Tumor location was intrahepatic in 47 patients (41.2%), extrahepatic in 27 (23.7%), gallbladder in 35 (30.7%) and ampulla of vater in 5 (4.4%). At the median follow-up duration of 10.7 months (95% CI, 8.2-13.2), 6-month OS rate was 58.1% in mFOLFOX and 46.0% in mFOLFIRI. Of 102 evaluable patients (mFOLFOX:51, mFOFIRI:51), objective response rate and disease control rate were 5.9% (95% CI, 0-12.4) and 64.7% (95% CI, 51.6-77.8) in mFOLFOX and 3.9% (95% CI, 0-9.2) and 58.8% (95% CI, 45.3-72.3) in mFOLFIRI. Median progression-free survival was 2.8 months (95% CI, 2.3-3.3) in mFOLFOX and 2.1 months (95% CI, 1.3-2.9) in mFOLFIRI (p = 0.682). Median OS was 6.6 months (95% CI, 5.6-7.6) in mFOLFOX and 5.9 months (95% CI, 4.3-7.5) in mFOLFIRI (p = 0.887). The most common grade 3/4 adverse events were neutropenia (26.3%) and AST/ALT elevation (15.8%) in mFOLFOX and neutropenia (24.6%) and anemia (17.5%) in mFOLFIRI. Peripheral neuropathy (36.8%) and thrombocytopenia (35.1%) in mFOLFOX and vomiting (19.3%) and cholangitis (10.5%) in mFOLFIRI occurred more frequently. No chemotherapy-related deaths were reported. Conclusions: In second-line treatment of BTC, mFOLFIRI was tolerable But, mFOLFIRI was not superior to mFOLFOX. Adverse events were different between two groups. Clinical trial information: NCT03464968 .

An exploratory study of fruquintinib as second-line treatment for patients with advanced or metastatic biliary tract cancer.

TPS4657 Background: Biliary tract cancer (BTC) is a relatively uncommon but highly fatal malignancy and most patients with BTC are diagnosed at advanced stages. Currently, no standard second-line treatment has been established following recurrence from the first-line treatment. VEGF is highly expressed in more than 50% of BTC, which indicates anti-angiogenesis might be a potentially effective method to improve the outcome in BTC. Fruquintinib is a novel small molecule tyrosine kinase inhibitor targeting VEGFR1, VEGFR2, and VEGFR3 and is currently being evaluated in clinical trials for multiple cancers including lung cancer, gastric cancer and colorectal cancer, and showed strong anti-tumor activity. However, the effect and safety of fruquintinib has not been investigated in the setting of second-line treatment for BTC. Methods: The study is a multicenter, single-arm, phase 2 trial of fruquintinib (5 mg, po, for 3 weeks, followed by 1 week off, 4 weeks for a cycle) for patients with advanced or metastatic BTC who have failed to first-line chemotherapy. The primary endpoint is progression-free survival (PFS) with the null hypotheses of 8 weeks, and the median PFS≥15 weeks as evidence of the study drug activity (α=0.05, 80% power, one-sided). The number of patients required to complete the study is 27. Allowing for 20% expulsion rate, the study needs 33 patients. The secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival (OS), safety and quality of life (QoL). Meanwhile, the study also set an exploratory objective to evaluate the mutation status of related genes in plasma (cfDNA) and tumor tissue and explore the interplay between mutation patterns with efficacy. Major eligibility requirements: Age ≥18 years; Histologically or cytologically confirmed diagnosis of advanced or metastatic biliary tract adenocarcinoma; First-line chemotherapy failed (tumor progression or intolerable adverse events); No less than 3 months of expected survival; ECOG PS≤1; At least one measurable lesion according to RECIST 1.1 criteria; Adequate organ function. Eligible patients with advanced or metastatic BTC refractory to first-line chemotherapy will be enrolled at 7 medical centers in China. The study is open and actively enrolling at time of submission. Clinical trial information: NCT04156958 .

FOLFIRI as second-line treatment of metastatic biliary tract cancer patients.

The combination of cisplatin and gemcitabine is the standard first-line treatment of metastatic biliary tract cancer (BTC) patients. The benefit of second-line chemotherapy in these patients is controversial. This study aims to evaluate the activity of FOLFIRI (fluorouracil and irinotecan) after failure to the first-line platinum and gemcitabine-based chemotherapy in metastatic BTC patients. We present a single-institution, retrospective cohort study. Patients with locally advanced or metastatic BTC who progressed after at least one line of chemotherapy, consecutively treated at our Institution between 2007 and 2017 were included. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), clinical benefit rate (CBR) and safety profile of FOLFIRI. Twelve patients were included in the analysis, with a median follow up of 5 months (95% CI 2.77-7.20). The median number of cycles received was 3 (range 1 to 9). Four grade 3 toxicities were recorded; no grade 4 toxicities and no treatment-related deaths occurred. The median PFS was 1.7 months (95% CI; 0.66-2.67), and median OS was 5 months (95% CI; 2.77-7.20). Two patients presented stable disease, providing a CBR of 17%. We concluded that FOLFIRI presented a favorable toxicity profile and a modest activity in metastatic BTC patients who had progressed to platinum and gemcitabine and may be considered in patients who are able to tolerate additional lines of chemotherapy. Immunotherapy and targeted therapies selected according to the tumoral genomic profile are promising alternatives to improve the outcomes of second-line treatment in BTC.