Results Of A Phase 3 Study Show TORISEL Significantly Improved Progression-free Survival For Patients With Relapsed/refractory Mantle Cell Lymphoma

Main Category: Lymphoma / Leukemia
Also Included In: Cancer / Oncology;  Clinical Trials / Drug Trials
Article Date: 09 Jun 2008 - 0:00 PDT

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Data presented from a phase 3 clinical trial at the 44th Annual Meeting of the American Society of Clinical Oncology show that patients with relapsed and/or refractory (failed front line therapy and unresponsive to most recent treatment) mantle cell lymphoma (MCL) treated with TORISEL (temsirolimus), an mTOR (mammalian target of rapamycin) inhibitor, experienced a statistically significant improvement (153 per cent) in median progression-free survival (PFS), compared with single-agent therapy selected by the investigator. TORISEL is currently approved in Canada for the treatment of metastatic (advanced) renal cell carcinoma (RCC).

Mantle cell lymphoma is a rare but deadly form of non-Hodgkin's lymphoma. In 2008, approximately 7,000 Canadians will be diagnosed with non-Hodgkin's lymphoma and over 3,000 will die from the disease in 2008.[i] Mantle cell lymphoma accounts for approximately six per cent of all non-Hodgkin's lymphoma cases.[ii]

Study Design and Results

This three-arm, open-label, randomized, phase 3 trial compared two different dose regimens of TORISEL with investigators' choice of therapy (IC) in patients with relapsed or refractory MCL who had received two to seven prior therapies, which could include hematopoietic stem cell transplantation.

Patients were randomly assigned to receive intravenous (IV) TORISEL at 175 mg for three successive weekly doses followed by 75 mg IV weekly; TORISEL 175 mg IV for three successive weekly doses followed by 25 mg IV weekly; or investigators' choice of one of the following single agents at predefined doses: gemcitabine, fludarabine, chlorambucil, cladribine, etoposide, cyclophosphamide, thalidomide, vinblastine, alemtuzumab or lenalinomide. The primary end point was PFS based on independent review. Secondary end points were objective response rate and overall survival.1

Median PFS for patients treated with TORISEL 175 mg/75 mg was 4.8 months, compared with 1.9 months for patients treated with IC (153 per cent improvement). In the TORISEL 175 mg/25 mg arm, median PFS was 3.4 months, but this difference was not statistically different from IC (P=0.0618).1

Patients receiving TORISEL 175 mg/75 mg showed a non significant trend toward longer overall survival than those treated with IC (10.9 months vs. 5.8 months, P=0.0714; HR=0.62). TORISEL 175 mg/75 mg led to a statistically significant improvement over IC in objective response rates (22 per cent vs. 2 per cent, P=0.0019).1

The most frequently occurring grade 3 or 4 adverse events among patients treated with TORISEL 175 mg/75 mg, TORISEL 175 mg/25 mg, or IC were thrombocytopenia (59 per cent vs. 52 per cent vs. 36 per cent patients, respectively), anemia (20 per cent vs. 11 per cent vs. 17 per cent), neutropenia (15 per cent vs. 22 per cent vs. 26 per cent) and asthenia (13 per cent vs. 19 per cent vs. 8 per cent).1

About TORISEL

TORISEL was approved by Health Canada in December 2007 and is the only mTOR inhibitor approved to treat advanced RCC. TORISEL specifically inhibits the mTOR kinase, an important regulator of cell proliferation, cell growth and cell survival[iii],[iv] and is the only renal cancer therapy proven to extend median overall survival compared with interferon-alpha in patients with advanced RCC.[v]

TORISEL is approved for the treatment of advanced RCC in Canada, the United States, European Union and other markets,9,[vi] based on results of a phase 3 clinical study that demonstrated that TORISEL improves overall survival for patients with advanced RCC compared with interferon-alpha.8

An application for the use of TORISEL for the treatment of relapsed and/or refractory MCL is currently under review with the European Medicines Agency (EMEA). TORISEL received Orphan Medicinal Product designation for the treatment of MCL in the European Union in November 2006.[vii]

Wyeth Pharmaceuticals

Wyeth is one of the world's largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing and marketing of pharmaceuticals, vaccines, biotechnology products and non-prescription medicines that improve the quality of life for people worldwide.

In partnership with the CIHR/Rx&D Collaborative Research Program, Wyeth Canada, has invested in a professional clinical research Chair in Oncology for a five year term. During this term, the Chair will be dedicated to Clinical Research in Oncology, specifically in kidney cancer with the aim of broadening scientific knowledge to address kidney cancer treatment issues in Canada.

Wyeth Pharmaceuticals

References

[i] National Cancer Institute of Canada. Canadian Cancer Statistics, 2008. Available here. Accessed May 26, 2008.

[ii] The Non-Hodgkin's Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. Blood. 1997;89:3909-3918.

[iii] Bjornsti MA, Houghton PJ. The TOR pathway: a target for cancer therapy. Nat Rev Cancer. 2004;4:335-348.

[iv] Janus A, Robak T, Smolewski P. The mammalian target of the rapamycin (mTOR) kinase pathway: its role in tumourigenesis and targeted anti-tumour therapy. Cell Mol Biol Lett. 2005;10:479-498.

[v] Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356:2271-2281.

[vi] TORISEL® (temsirolimus) Summary of Product Characteristics, Wyeth Pharmaceuticals.

[vii] Commission of the European Communities. Commission Decision of 06-XI-2006 relating to the designation under Regulation (EC) No 141/2000 of the European Parliament and of the Council of "Temsirolimus" as an orphan medicinal product. Available here. Accessed Dec. 12, 2007.

Wyeth Pharmaceuticals