The ABC-06 study – first results out …
The first results of the ABC-06 clinical trial were formally presented by Dr Angela Lamarca of The Christie NHS Foundation Trust at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago on 2nd June 2019.
ASCO hosts the largest global cancer conference with over 45,000 attendees, and the ABC-06 trial results were presented in front of an audience of approximately 5,000.
Dr Angela Lamarca, The Christie NHS Foundation Trust and the University of Manchester, speaks to the ASCO Post about the ABC-06 trial after presenting the results at the 2019 ASCO Annual Meeting
Background to ABC-06
Patients with advanced biliary tract cancer (ABC) are usually first treated with two chemotherapy drugs called cisplatin and gemcitabine which since 2010 when the ABC-02 trial reported positively, has been the first line ‘standard of care’ for patients with ABC.
The ABC-06 trial was carried out to find out whether patients should be treated with different chemotherapy after they have already been treated with cisplatin and gemcitabine if their disease becomes resistant to this treatment. This is called ‘second line’ therapy.
What is active symptom control?
Usually, following the standard first line treatment, patients are offered ‘best supportive care’, which can vary from hospital to hospital. The main priority in these patients, is to control the symptoms of the cancer as much as possible, and does not include more cancer treatment. The ABC-06 trial carefully described how these patients should be monitored and what action should be taken if symptoms were identified. This is called active symptom control and is a more proactive approach than best supporting care. Patients were reviewed in clinic every 4 weeks for early detection and treatment of biliary-related complications. This included (but was not limited to); improving bile duct drainage and the use of antibiotics, pain control, steroids or sickness control.
This study began recruiting patients in early 2014 from 20 UK hospitals. However, it took longer to recruit patients than expected and, as AMMF recognised the importance of this trial, the charity provided financial assistance to enable the trial to complete.
The 162 patients in this study had previously-treated ABC which had worsened, but who were otherwise fit and well. All patients received active symptom control (which involved closer monitoring than the current standard NHS practice of best supportive care). Half the patients also received chemotherapy treatment (Oxaliplatin, L-folinic acid and 5-fluorouracil – abbreviated to mFOLFOX) every 14 days up to 12 times.
ABC-06 was sponsored by The Christie NHS Foundation Trust and was run by the Manchester University clinical trials unit with Professor Juan Valle as the Chief Investigator. The majority of the funding was provided by Cancer Research UK, with additional funding from AMMF, Stand Up to Cancer, The Cholangiocarcinoma Foundation and The Christie Charitable Fund.
In order to work out which group of patients fared best, careful comparisons were made of the similarities and differences. The main comparisons made between the two groups of patients were to compare how long patients lived for and how bad the side-effects were. Other comparisons which have not yet been completed include checking on quality of life, how much the treatments cost, and laboratory testing of blood and tumour samples collected from patients. This information will be reported once it is available.
Results and conclusions
Clinical trial results usually report the median (or middle value of each treatment group) amount of time that patients were alive for, the median overall survival. For the patients who received active symptom control alone, this was 5.3 months, whereas those patients who had also received the chemotherapy survived for 6.2 months.
This does not sound like a big improvement for those patients who received chemotherapy (they lived less than one month longer). It is important to understand that patients in the active symptom control group lived longer than expected. This shows the benefit of actively looking for and where possible actively managing symptoms. This plan (which involved reviewing these patients every 4 weeks in clinic) meant that these patients lived longer than previous reports of best supportive care (around 4 months).
The data also shows that after a year, only 1 in 10 of the patients in the active symptom control group were still alive, but 1 in 4 of the patients who had chemotherapy were still alive. The benefit of chemotherapy appeared similar in patients with different types of ABC.
The side-effects were not dramatically different between the two groups of patients (some of the symptoms reported are probably due to the cancer rather than the treatment). 40% of patients who received active symptom control and 59% of patients who also received chemotherapy reported the most serious grades of side-effects. Three patients are known to have died as a result of their chemotherapy.
This is the first study that tested the benefit of further chemotherapy in patients with ABC, after their disease has become worse during or after treatment with cisplatin and gemcitabine.
Patients who received active symptom control alone lived longer than expected, demonstrating the value of this over a less well defined ‘best supportive care’ approach.
Patients who also received mFOLFOX chemotherapy (as well as best supportive care) lived longer and more of these patients were alive one year later, than patients who received best supportive care alone.
Quality of life, health economic evaluation and laboratory research is ongoing and will be reported as soon as the results are available.
This is called a practice-changing clinical trial; mFOLFOX chemotherapy combined with active symptom control should become standard of care (for everyone in the world) for second-line treatment of patients with ABC.
Helen Morement, CEO of AMMF, comments on the ABC-06 results:
“The annual incidence of biliary tract cancers has risen steeply and steadily across the world over past years. In 2013, bile duct cancer (cholangiocarcinoma) and gall bladder cancer were the cause of 2,599 deaths in England alone (bile duct cancer: 2161; gallbladder cancer: 438)1. While survival statistics for many other cancers show recent significant improvement, with very little in the treatment armoury for biliary tract cancers, fewer than one in 20 of these patients survive five years after diagnosis. A truly devastating situation and one that hasn’t improved in decades.
“The positive outcome of the ABC-06 trial, showing an albeit modest survival improvement, is certainly welcomed by AMMF as this will mean there is now a treatment for those patients for whom, until this point, there was no proven second line treatment. It is also significant that those on active symptom control alone lived longer than expected, demonstrating the value of this for patients over the ‘best supportive care’ approach currently used within the NHS.
And, importantly, the success of this study could help inform the direction of future studies.”