A major announcement Sunday at ASCO was that Merck and AstraZeneca are to partner on a Phase I cancer trial in which drugs from both companies will be tested in combination. This may not seem it but it is a landmark moment, and validation of the trend seen at ASCO which is that combining targeted drug therapies is likely to be the future of tumor management,and will require partnering by many more companies.
One session on Monday reviewed new drugs currently in Phase I safety testing and which target the mTOR pathway and related Ras pathway elements – which is of major interest in neurofibromatosis. These drugs were assessed for safety in a variety of solid tumors, but these early stage studies also revealed the when dosed daily or every other day at fairly modest doses, drugs are showing promise to be safe and also reach the tumors, and shrink them and/or stabilize the disease. Drugs discussed included GDC0941 (a pan PI3 kinase inhibitor), XL765 targets (PI3 kinase, Torc 1 and Torc 2) and MK2206 (a pan Akt inhibitor). All of these drugs could be of potential future interest for neurofibromatosis therapies so we will be monitoring them closely.
Cancer patients can now access unlimited online information about drugs in clinical trials. Armed with this, some patients have advocated for the right to have immediate and direct access to emerging drugs ‘off label’ before clinical trials are completed. There may be good cause for this: if all other options for therapy are exhausted; if patient is not eligible for any clinical trial protocols; and if there is enough information that toxicity is not a concern and there is a reasonable chance of some efficacy. This has become a hot button issue and was the theme of a session at ASCO on Monday with speakers from the clinician, ethical and patient advocate perspectives. It is understandable that patients want accelerated access to drugs, but many issues need to be considered. Though clinical trials might seem to some patients like a blockade to drug access, they are an important part of figuring out if a drug is safe and effective. If drugs are made more freely available ‘off label’ before trials are fully completed, this could lead to unprecedented side effects (as happened as a result of off-label breast cancer trials in the 1990s) or even to a drug company sponsor using data from off-label uses to promote a drug prematurely. In addition, insurance could be a concern. A small informal survey of physicians reported at ASCO showed that 80% of doctors have given drugs to patients off-label. However there are no national guidelines on this. As the number of drugs available looks set to increase, one recommendation of this session was that ASCO develop policy guidelines for doctors to address when it is appropriate to prescribe off label.
