The analysis of two Phase III trials of Torisel (temsirolimus), now approved for the treatment of advanced renal cell carcinoma (RCC), was presented on Saturday at the 43rd American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, US. The results showed that the new drug improves overall survival rates and also quality of life, compared to patients treated with interferon-alpha.
Renal cell carcinoma accounts for approximately 85 per cent of kidney cancers. The American Cancer Society estimates that 51,190 new cases of kidney cancer will be diagnosed this year, and more than 40 per cent of patients will only be diagnosed once the disease is already at an advanced stage.
When the US Food and Drug Administration (FDA) allowed doctors to being prescribing Torisel last week, the drug became the first marketed therapy that inhibits mammalian target of rapamycin (mTOR), a key protein in cells that regulates cell proliferation, cell growth and cell survival.
This latest analysis showed that Torisel increased overall survival and progression-free survival regardless of tumour cell type compared to interferon-alpha. For clear-cell tumours, the most common form of RCC, the overall survival time increased 30 per cent, from 8.2 months to 10.6 months and progression-free survival increased from 3.8 to 5.5 months.
For patients with other tumour cell types, differences in overall survival and progression-free survival were even greater for Torisel patients, compared to those treated with interferon-alpha. Overall survival was more than twice as long - 11.6 months from 4.3 months - and progression-free survival increased by nearly four times on average, from 1.8 months to 7.0 months.
The positive results for Wyeth will also come as a boost for other companies developing mTOR inhibitors, such as Exelixis and Ariad Pharmaceuticals. The latter company have the more advanced programme with AP23573 having completed several Phase II trials and is due to start Phase III trials for metastatic sarcoma this year. Ariad is currently "completing negotiation with a major pharmaceutical company" to partner the development of the drug.
Novartis' everolimus (RAD001) is also an mTOR inhibitor that is currently in Phase I and II trials for several tumour types, including breast, lung, neuroendocrine and gastrointestinal stromal tumour (GIST).
On the down-side, there are some serious side-effects associated with this new class of cancer medication. Wyeth said that using Torisel is likely to result in increases in serum glucose, which may result in the need for an increase in the dose of, or initiation of, insulin and/or oral hypoglycaemic agent therapy. The drug may also have an immunosuppressant effect. Cases of interstitial lung disease, some resulting in death have also occurred. However, the most common side effects are rash, asthenia, mucositis, nausea, oedema, and anorexia.
The approval of Torisel represents the seventh New Molecular Entity application passed by the FDA this year, although one of those was previously approved in Europe. The others are: New River Pharamceuticals' Vyvanse (lisdexamfetamine); Novartis and Speedel's Tekturna (Aliskiren); GlaxoSmithKline's Tykerb (lapatinib) and Altabax (retapamulin); and Alexion Pharmaceuticals Soliris (eculizumab). Schwarz Pharma's Neupro (rotigotine) was also approved as an NME by the FDA having already been approved by the European Medicines Agency (EMEA).