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Second-Line FOLFOX May Become ‘Standard Of Care’ For Advanced Biliary Tract Cancer

Phase III trial findings indicate a survival advantage for advanced biliary tract patients who receive second-line FOLFOX chemotherapy alongside active symptom control
01 Apr 2021
Anticancer Agents;  Gastrointestinal Cancers;  Hepatobiliary Cancers;  Therapy

Author: By Lynda Williams, Senior medwireNews Reporter


medwireNews: The addition of second-line folinic acid, fluorouracil and oxaliplatin (FOLFOX) chemotherapy to active symptom control (ASC) offers a significant overall survival (OS) benefit for patients with advanced biliary tract cancer, report the ABC-06 investigators.

“To our knowledge, this trial is the first prospective, randomised study providing reliable, high-quality evidence to allow an informed discussion with patients of the potential benefits and risks from second-line FOLFOX chemotherapy in advanced biliary tract cancer”, say Juan Valle, from The Christie NHS Foundation Trust in Manchester, UK, and colleagues.

“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”, they recommend in The Lancet Oncology.

The phase III open-label trial included 162 patients with locally advanced or metastatic biliary tract cancer, including cholangiocarcinoma and gallbladder or ampullary carcinoma, who had previously progressed on first-line cisplatin plus gemcitabine.

After a median follow-up of 21.7 months, median OS was 6.2 months for the 81 patients who were randomly assigned to receive up to 12 cycles of FOLFOX given at 2-week intervals alongside ASC, which consisted of early identification and treatment of biliary-related complications and cancer-related adverse events, such as drainage, palliative radiation and pain relief.

The OS in these patients was significantly longer than the median 5.3 months achieved by the 81 patients who received only ASC, giving a hazard ratio (HR) for death of 0.69 in favour of FOLFOX use, the investigators say.

At 6 months, 50.6% of patients given FOLFOX plus ASC were alive compared with 35.5% of those given only ASC, with corresponding 12-month rates of 25.9% and 11.4%.

“We cannot exclude that ASC in the chemotherapy group was more meticulous than in the ASC alone group, but we considered fortnightly visits for patients not receiving chemotherapy too onerous; moreover, this is unlikely to have had a substantial effect on overall survival”, remark Juan Valle et al.

Median progression-free survival in the FOLFOX plus ASC arm was 4.0 months, with 66.7% free from progression at 3.0 months, falling to 32.1% at 6.0 months and 8.6% at 12.0 months. There was one complete response and three partial responses in this arm, with disease control reported for 33.0%. At the time of reporting, three patients remained free from disease progression after 13.3–18.4 months, the researchers say.

In the chemotherapy arm, patients received a median five cycles of FOLFOX and just 16% of patients completed all 12 cycles; 61% required at least one dose reduction or cycle omission, with discontinuation most commonly attributed to disease progression, intolerable toxicity or illness.

Patients given FOLFOX plus ASC had a higher rate of grade 3–5 adverse events than those given ASC alone, at 69% versus 52%. FOLFOX was most commonly associated with grade 3–5 neutropenia (12%), fatigue or lethargy (11%) and infection (10%) and there were three chemotherapy-related deaths from infection, febrile neutropenia and acute kidney injury.

“The toxicity profile of FOLFOX was tolerable and in line with that described with FOLFOX in many other malignancies”, Juan Valle et al comment.

Discussing their findings, the researchers admit that “[t]he benefit achieved with the addition of FOLFOX chemotherapy in terms of median overall survival might seem marginal (lessened by a better than expected overall survival in the ASC alone group)”, but emphasize that “this finding has also been described in other studies in this setting and might reflect the rapid deterioration of some patients before treatment has time to have a biological effect.”

Moreover, they believe that “the overall reduction in risk of death and positive impact on 6-month and 12-month overall survival rates are clinically meaningful.”


Lamarca A, Palmer DH, Wasan HS, et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol; Advance online publication 30 March 2021. doi:10.1016/S1470-2045(21)00027-9

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2021 Springer Healthcare part of the Springer Nature group

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