Targeted cancer therapies: Another step forward

While it is clear that the treatment of cancer has already begun to undergo a paradigm shift with the inclusion of innovative targeted therapies into current regimens, it would be wrong to assume these products will entirely replace traditional chemotherapy as the standard treatment for cancer sufferers. However, the administration of targeted therapies alongside standard chemotherapy should allow for improvements in symptom control, quality of life and cure rates, although according to a new report from independent market analyst Datamonitor* (DTM.L), this will not be without significant challenges.

Provide potential

Datamonitor defines innovative targeted therapies as novel therapeutic agents that target unique molecular changes which distinguish tumor cells from normal cells, namely altered genes, proteins and corrupted molecular pathways. The major upside of enhanced selectivity in targeting tumor-specific molecular abnormalities is that they provide the potential for the creation of treatments with enhanced efficacy and reduced toxicity.

The existing targeted therapies market was worth $5.1 billion across the seven major pharmaceutical markets** in 2004. Datamonitor forecasts this market to reach $13.7 billion in value by 2014, achieving a compound annual growth rate (CAGR) of 13.7%. Furthermore, the introduction of current late-phase pipeline products will increase the targeted therapies market's total value to a figure of $19.2 billion by 2014, says Datamonitor oncology analyst Fleur Pijpers. 'Growth of the current targeted therapies market will be driven mainly by five key products: Genentech/Roches Rituxan (rituximab), Herceptin (trastuzumab), Avastin (bevacizumab), Tarceva (erlotinib) and Novartis's Glivec (imatinib).'

'Rituxan and Glivec have already reached blockbuster status, while Herceptin, Avastin and Tarceva are forecast to also achieve sales exceeding $1 billion per year by 2014.'

Datamonitor believes the continued sales growth of these targeted therapies is attributable to a number of factors: (all figures for seven major markets)

Rituxan will enjoy label expansion and increased market penetration, with forecast sales of $3.6 billion by 2014.

Herceptin will move into the adjuvant treatment setting for breast cancer, with forecast sales of $1.2 billion by 2014.

Avastin's activity in non-small cell lung cancer (NSCLC), breast cancer, prostate cancer, renal cell carcinoma and pancreatic cancer is expected to garner further regulatory approvals, with forecast sales of $2.4 billion by 2014.

Glivec will enjoy increased uptake due to alternate dosing schedules and approvals in further indications, with forecast sales of $2.7 billion by 2014.

While Tarceva will benefit from AstraZeneca's Iressa's (gefitinib) failures following US and EU approvals for NSCLC and recent US approval for pancreatic cancer, with forecast sales of $1.1 billion by 2014.

Active pipeline

Not surprisingly, the targeted therapies pipeline is currently an area of dynamic clinical activity, a trend that is likely to continue for many years. The overall pipeline currently contains at least 168 investigational compounds, constituted by 28% angiogenesis inhibitors, 25% signal transduction inhibitors, 17% apoptosis stimulators, 17% monoclonal antibodies, 7% cell cycle regulators and 6% histone deacetylase inhibitors.

Datamonitor, supported by opinion leader interviews, determines that the signal transduction inhibitors and angiogenesis inhibitors provide the most significant opportunity for development and commercialization in the short to medium term. Many of these agents confer the ability to inhibit multiple targets, showing applicability for use across a range of tumor types and increased efficacy, Pijpers says. 'Many compounds within these two drug classes present small molecule formulations, allowing for oral availability and greatly reduced toxicity.'

Most targeted therapies confer greater clinical benefit when administered in combination with standard chemotherapy, rather than as a single agent. However, combining several different classes of drugs will result in 'cocktail' therapies for cancer, which brings to light the problem of cumulative toxicity, which will increase in line with the number of agents in the 'cocktail'. This issue is being overcome, however, by the development of products such as Onyx Pharmaceuticals/Bayer's sorafenib (Nexavar) and Pfizer's Sutent (SU11248), which inhibit multiple pathways, Pijpers says. 'In addition, if fewer products are included in a 'cocktail' therapy, the problem of escalating treatment costs, complex clinical trials and prolonged development is also overcome somewhat.'

Selection vital

In order to improve uptake of targeted therapies, some of which will undoubtedly be expensive, it is argued that patient selection must be improved, in order to identify those cohorts who will derive most benefit from specific products. A shift is occurring away from the traditional anatomical classification of a malignancy to a system that differentiates tumors on the basis of molecular aberration, Pijpers says. 'The archetypical example of this approach is that used in the development and launch of Genentech/Roche's Herceptin (trastuzumab), which enrolled patients into clinical trials based on HER-2 status. This approach cannot be employed, however, without the identification of molecular markets predictive of tumor response and subsequent development of diagnostics to define patient populations.'

So while targeted therapies are and will become even more so, a valuable and effective weapon in the fight against cancer, they will compliment rather replace existing chemotherapy regimes. And they are most certainly not a cancer 'cure' as has been touted in some quarters.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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