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The study results, according to the authors, suggest that the combination of folinic acid plus the chemotherapies fluorouracil and oxaliplatin should become the standard-of-care therapy in patients with advanced biliary tract cancer whose disease progressed with cisplatin and gemcitabine.
Treatment with folinic acid plus the chemotherapies fluorouracil and oxaliplatin (FOLFOX) along with active symptom control (ACS) in patients with advanced biliary tract cancer whose disease progressed after first-line treatment with the chemotherapies cisplatin and gemcitabine was associated with improved survival, compared to ACS alone.
The data, which were recently published in Lancet Oncology, demonstrate that FOLFOX should become the second-line standard-of-care chemotherapy option for this patient population, according to the study authors.
They noted that although some clinicians have treated patients with FOLFOX after their disease has progressed, there is limited data on the efficacy of the second-line chemotherapy after patients failed initial treatment with cisplatin and gemcitabine.
“Patients with advanced biliary tract cancer often experience a rapid decline in performance status following progression on first-line chemotherapy, and only 15% to 25% receive second-line therapy,” they wrote. “Some studies suggest that second-line chemotherapy might be of value for patients with a good performance status; however, this theory is subject to selection bias and has not been explored in a randomized study, and no consensus exists regarding the optimum regimen.”
To assess if adding FOLFOX to ASC following disease progression after treatment with cisplatin and gemcitabine was beneficial for patients, the study authors randomized 162 patients to receive either ASC alone (81 patients) or FOLFOX plus ASC (81 patients).
All patients enrolled onto the trial had a diagnosis of advanced or metastatic biliary tract cancer, which included cholangiocarcinoma (117 patients) and gallbladder (34 patients) or ampullary cancer (11 patients) with documented radiological disease progression after first-line cisplatin and gemcitabine.
FOLFOX was given intravenously every two weeks for a maximum of 12 cycles, six weeks after disease progression to the first-line treatment. ASC consisted of the early identification and treatment of biliary-related complications and the management of cancer-related symptoms. These methods included, but were not limited to, treatment with antibiotics, steroids, palliative radiotherapy and anti-nausea medications.
After a median follow-up of 21.7 months, the data demonstrated that the median overall survival among patients who received ACS plus FOLFOX was 6.2 months compared to 5.3 months for those who received ACS alone. Moreover, the authors reported that patients treated with FOLFOX plus ASC had an overall survival rate of 50.6% at six months and 35.5% at 12 months compared to 25.9% and 11.4% in the ASC alone group.
“The overall reduction in risk of death and positive impact on six-month and 12-month overall survival rates are clinically meaningful,” the authors wrote.
The study results showed that 69% of patients in the ASC plus FOLFOX group reported serious or severe side effects such as neutropenia, fatigue, lethargy and infection. There were also three chemotherapy-related deaths. Fifty-two percent of patients in the ASC alone group reported experiencing serious or severe side effects.
“(This) study showed how the overall survival and progression-free survival benefit was independent of whether patients were classed as being platinum sensitive or platinum refractory or resistant,” authors wrote. “In fact, subgroups with suspected poorer prognosis seemed to benefit most from FOLFOX. A potential explanation is that those patients with more aggressive tumors are the ones deriving more benefit from an aggressive antiproliferative therapy such as second-line chemotherapy.”
By the time of data analysis, 78 of the 81 patients assigned to receive ASC plus FOLFOX had disease progression or had died. The authors observed that there was a median progression-free survival (time between study randomization and disease progression or death of any cause) of 4 months, with a 66.7% rate at three months, 21.1% at six months and 8.6% at 12 months. Out of the 81 patients in the group, disease control was observed in 27 – which included 23 patients with stable disease. The authors noted that the remaining 53 patients were non-responders, whether due to disease progression or death.
“The addition of FOLFOX to ASC improved median overall survival in patients with advanced biliary tract cancer after progression on cisplatin and gemcitabine, with a clinically meaningful increase in six-month and 12-month overall survival rates,” they concluded. “Based on these findings, FOLFOX should become standard-of-care chemotherapy in second-line treatment for advanced biliary tract cancer and the reference regimen for further clinical trials.”
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