Nav: Home

Ibrutinib in CLL: Added benefit for treatment-naive patients not proven

October 10, 2016

Ibrutinib was approved in 2014 for the treatment of certain adults with chronic lymphocytic leukaemia (CLL), particularly as second-line treatment. The therapeutic indication was expanded in 2016. The drug is now also approved for treatment-naive patients. The German Institute for Quality and Efficiency in Health Care (IQWiG) has now examined in a dossier assessment whether this drug offers an added benefit. This was not proven, however, because the drug manufacturer presented no suitable data for any of the total of three subgroups of patients.

G-BA defined three research questions

The Federal Joint Committee (G-BA) distinguished between three treatment situations in its commission and specified a different appropriate comparator therapy for each of them: In patients for whom chemo-immunotherapy is an option and for whom a combination therapy consisting of fludarabine, cyclophosphamide and rituximab (FCR) is also suitable, ibrutinib was to be compared with FCR. If chemo-immunotherapy is an option, but FCR is not, ibrutinib was to be tested against chemo-immunotherapy at the physician's choice.

The third research question concerned treatment-naive CLL patients for whom chemo-immunotherapy is not an option. In this patient group, ibrutinib was to be compared with best supportive care (BSC). BSC means the best possible supportive therapy, optimized for the individual patient for alleviation of symptoms and improvement in the quality of life. Patients with specific mutations (17p deletion, TP53 mutation) were not subject of this assessment because ibrutinib has already been approved for them for a longer period of time.

Studies not sufficiently similar

For the first research question, the dossier contained no data at all. For the second patient group, for whom FCR is not an option, the manufacturer presented results from indirect comparisons because no studies of direct comparisons were available.

Sufficient similarity of the studies was not ensured in any of these indirect comparisons, however. In particular, the dosage of the drug differed in the respective comparator arms, and was partly too low. In addition, treatment did not comply with the approval in some of the patients. Furthermore, the participants differed regarding different aspects including age and accompanying diseases. It could therefore not be excluded that differences in the treatment results were solely caused by differences in dosage or the study populations.

Best supportive care not implemented

For the third research question, the manufacturer used a study of direct comparison. Its results were unsuitable for the assessment of the added benefit, however, because the study also included patients for whom an alternative chemo-immunotherapy would have been an option. In addition, all participants in the comparator arm received the identical drug. This means, however, that treatment was not optimized for the individual patient.

Hence the dossier contained no data that would be suitable for the assessment for any of the three research questions. An added benefit of ibrutinib in comparison with the respective appropriate comparator therapy is therefore not proven in the expanded therapeutic indication either.

G-BA decides on the extent of added benefit

The dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the G-BA. After publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.
-end-
More English-language information will be available soon (Sections 2.1 to 2.6 of the dossier assessment as well as easily understandable information on informedhealth.org). If you would like to be informed when these documents are available, please send an e-mail to info@iqwig.de.

Institute for Quality and Efficiency in Health Care

Related Comparator Therapy Articles:

Radiation therapy, macrophages improve efficacy of nanoparticle-delivered cancer therapy
Massachusetts General Hospital investigators report finding finding how appropriately timed radiation therapy can significantly improve the delivery of cancer nanomedicines by attracting macrophages to tumor blood vessels, which results in a transient 'burst' of nanoencapsulated drugs from capillaries into the tumor.
Lipid nanoparticles for gene therapy
Twenty-five years have passed since the publication of the first work on solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) as a system for delivering drugs.
Pet therapy can combat homesickness
The expression dog is man's best friend might have more weight in the case of first-year university students suffering from homesickness, according to a new UBC study.
On the path to controlled gene therapy
The ability to switch disease-causing genes on and off remains a dream for many physicians, research scientists and patients.
Transplantation and cell therapy
Key leaders in the field of cellular therapy will highlight new applications to potentially cure patients with blood diseases and infections on the occasion of the 5th Cell Therapy Day.
Benefit of extending anticoagulation therapy lost after discontinuation of therapy
Among patients with a first episode of pulmonary embolism (the obstruction of the pulmonary artery or a branch of it leading to the lungs by a blood clot) who received six months of anticoagulant treatment, an additional 18 months of treatment with warfarin reduced the risk of additional blood clots and major bleeding, however, the benefit was not maintained after discontinuation of anticoagulation therapy, according to a study in the July 7 issue of JAMA.
Japanese Society for Dialysis Therapy to publish Renal Replacement Therapy with BioMed Central
BioMed Central is pleased to partner with the Japanese Society for Dialysis Therapy in publishing the open-access journal Renal Replacement Therapy.
Can light therapy help the brain?
An innovative therapy that applies red and near-infrared light to the brain is now being tested at the Boston VA for Gulf War Illness, traumatic brain injury, and PTSD.
Not all EGFR mutations are the same when it comes to therapy for NSCLC
Certain rare epidermal growth factor receptor mutations are associated with tobacco smoking, worse prognosis and poor response to EGFR tyrosine kinase inhibitor therapy compared to the more common 'classical' EGFR mutations.
Clinical trial shows benefits of animal-assisted therapy in adult cancer patients undergoing complex cancer treatment with chemotherapy and radiation therapy
Therapy dogs may improve the emotional well-being of some cancer patients, according to results of a clinical study, the first to document the benefits of animal-assisted therapy in adult cancer patients.

Related Comparator Therapy Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Jumpstarting Creativity
Our greatest breakthroughs and triumphs have one thing in common: creativity. But how do you ignite it? And how do you rekindle it? This hour, TED speakers explore ideas on jumpstarting creativity. Guests include economist Tim Harford, producer Helen Marriage, artificial intelligence researcher Steve Engels, and behavioral scientist Marily Oppezzo.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".