Roche (SIX: RO, ROG; OTCQX: RHHBY) announced positive data from a Phase III study of Rituxan/MabThera (rituximab) in patients with advanced follicular lymphoma who did not have symptoms of disease (asymptomatic disease). Based on results of previous studies(1) that showed no benefit of immediate chemotherapy after diagnosis, asymptomatic patients are managed by a "watchful waiting" approach and treatment for these patients usually does not begin until specific symptoms occur or their disease worsens. This study showed that immediate administration of single-agent Rituxan/MabThera (induction), followed by continued use of Rituxan/MabThera (maintenance) delayed the need for chemotherapy or radiotherapy and decreased the risk of the disease worsening (progression-free survival or PFS), compared to watchful waiting. The safety profile was consistent with previous experience with Rituxan/MabThera.
The data were featured during a press briefing at the 52nd Annual Meeting of the American Society of Hematology (ASH) in Orlando, FL.
"We have found another way of managing this disease in its early years," said Dr Kirit Ardeshna, University College Hospital, London, UK and Chief Investigator for the Watch and Wait trial. "For many patients it is important to delay the onset of chemotherapy and for them the results of this study is a great advance."
The Phase III results showed that immediate use of Rituxan/MabThera monotherapy as induction followed by maintenance when compared to watchful waiting, decreased the risk of needing additional therapy by 80% (hazard ratio of 0.20, 95% CI, 0.13-0.29, p <0.001) and decreased the risk of their disease worsening (progression-free survival - PFS) by 79% (based on a hazard ratio of 0.21, 95% CI, 0.15-0.29, p <0.001). The median time to initiation of new therapy (chemotherapy or radiotherapy) for patients managed by watchful waiting was 34 months and the median PFS was 23 months. However, in patients given immediate Rituxan/MabThera followed by maintenance, the median of these parameters was significantly longer (p value of <0.0001) and has not been reached after four years.
"These are the first Phase III data to have shown that initial use of Rituxan/MabThera monotherapy as induction followed by maintenance had an impact in patients with asymptomatic follicular lymphoma, a disease that is commonly treated only after symptoms appear," said Hal Barron, M.D., Head of Global Development and Chief Medical Officer of Roche. "Early treatment interventions in prior studies in this population were not considered to provide meaningful clinical benefit. In this study, the use of Rituxan/MabThera delayed the need for additional treatment."
The data from the watch and wait study add to a growing body of evidence supporting Rituxan/MabThera induction and maintenance as an important strategy in follicular lymphoma. Rituxan/MabThera was recently approved in the EU for use in previously untreated patients who responded to induction therapy. The approval was based on results from the PRIMA study which included patients with advanced symptomatic follicular lymphoma, and showed that patients who continued Rituxan/MabThera therapy after having responded to initial Rituxan/MabThera plus chemotherapy had a nearly doubled likelihood of living without their disease worsening (PFS). Further data updates from the PRIMA study and another Rituxan/MabThera maintenance study called MAXIMA will also be presented at ASH.
About the "Watch and Wait" study
Sponsored by University College London Hospitals, this Phase III study was an international, multicenter, randomized, trial that enrolled 462 patients with previously untreated asymptomatic Stage II-IV follicular lymphoma. The trial compared the safety and efficacy profile of first-line induction followed by maintenance use of Rituxan/MabThera alone (four weekly doses followed by maintenance doses once every 2 months for two years) compared to careful observation (i.e.: watchful waiting). Patients were randomized to receive one of the following:
- Arm A: No therapy / watchful waiting
- Arm B: Rituxan/MabThera alone (rituximab375mg/m2 weekly) for four cycles only (without maintenance Rituxan/MabThera)
- Arm C: Rituxan/MabThera alone (rituximab375mg/m2 weekly) for four cycles followed by Rituxan/MabThera maintenance, given once every two months for two years.
Three years after the enrollment of the first patient, the Rituxan/MabThera arm that did not include maintenance (Arm B) was closed because of emerging evidence of Rituxan/MabThera's efficacy in the maintenance setting. The trial was then amended to compare Rituxan/MabThera maintenance following initial use of Rituxan/MabThera alone to watchful waiting (Arm C compared to Arm A).
About Follicular Lymphoma
Follicular lymphoma (FL), a cancer of the blood, is a common type of non-Hodgkin's lymphoma (NHL) which is slow-growing and is characterized by periods of relapse and remission. Follicular lymphoma unfortunately remains incurable and despite substantial progress, patients ultimately relapse and relapses require additional treatments Approximately 286’000 people worldwide are diagnosed with NHL each year(2), and FL accounts for about one in five of these cases. Follicular lymphoma can occur at any time during adulthood, though people are typically diagnosed during their fifties and sixties, affecting both men and women.
About Rituxan/MabThera
Rituxan/MabThera is a therapeutic antibody that binds to a particular protein - the CD20 antigen - on the surface of normal and malignant B-cells. It then recruits the body's natural defences to attack and kill the marked B-cells. Stem cells (B-cell progenitors) in bone marrow lack the CD20 antigen, allowing healthy B-cells to regenerate after treatment and return to normal levels within several months.
Rituxan/MabThera, discovered by Biogen Idec, first received FDA approval in November 1997 for the treatment of relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent. It was approved in the EU under the trade name MabThera in June 1998. Over 2.1 million patient exposures with Rituxan/MabThera have been recorded worldwide since launch, 2.0 million in haematological malignancies.
MabThera is known as Rituxan in the United States, Japan and Canada. Genentech and Biogen Idec collaborate on Rituxan in the United States, and Roche markets MabThera in the rest of the world, except Japan, where MabThera is co-marketed by Chugai and Zenyaku Kogyo Co. Ltd.
About Roche
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world's largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche's personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2009, Roche had over 80'000 employees worldwide and invested almost 10 billion Swiss francs in R&D. The Group posted sales of 49.1 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.
1. Ardeshna et al. Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. The Lancet, Vol 362, August 16, 2003: 516-522
2. http://www.lymphomacoalition.org accessed September 2010