This year ASCO celebrates 50 years of fighting cancer, and drug development has changed significantly during this time. For a long time, cancers were treated using chemotherapy alone, using a "one size fits all" approach. While chemotherapy is still the mainstay of treatment for many cancers, newer targeted therapies some of which are biomarker driven are becoming ever more prominent in the oncologists' armamentarium.
With the increase in approvals of more targeted and efficacious therapies, the drug development cycle has had to adapt accordingly. Historically, the phases of drug development have been well defined, with Phase I studies determining the maximum tolerated dose, Phase II studies show signs of efficacy, ultimately leading to a randomized Phase III clinical trial against a comparator and hopefully regulatory approval. However, the different phases of clinical development have recently become more blurred, for example Merck & Co enrolled more than one thousand patients across multiple solid tumor types in a Phase I trial for MK-3475 (pembrolizumab), and the FDA has conditionally approved drugs with single arm Phase II studies (e.g. Pharmacyclics Imbruvica). Furthermore, there is a lot of debate on whether to incorporate a biomarker in the early or late stages of drug development. For example, cetuximab (ImClone/Merck Serono/Bristol-Myers Squibb's Erbitux) only has its KRAS biomarker defined after it had already been approved for colorectal cancer, whilst many other investigational drugs have required only certain patients with specific tumor molecular characteristics to be enrolled on clinical studies. The drug development pathway will become even shorter, due to in part more companies taking advantage of the FDA's Breakthrough Therapy Designation and Fast Track processes.
Finally as more drugs become approved for cancer treatment, the "low hanging fruit" becomes ever harder to grab. Therefore nimbleness and having an open mind during the drug development cycle will become ever more important. Furthermore, different clinical trial endpoints must be considered for newer therapies with increasingly diverse mechanisms of action. For example, tumor response is a good predictor of efficacy for cytotoxic therapies, but is not as good predictor of efficacy for newer immunotherapies, such as the anti-PD1 and anti-CTLA4 checkpoint inhibitors. As cancer becomes an ever increasingly more chronic disease, there will be an increased emphasis in quality-of-life data, as well as the cost-effectiveness of these therapies.
This year at ASCO data from a whole host of studies are being presented; many are practice changing. As we move into a new era of clinical oncology practice, the old rules of drug development become ever more outdated. Therefore clinicians, industry, and academia will have to work ever closer together to further the progress in developing cancer treatment over what has already been achieved, to ultimately provide the best outcome for patients.
Dan Roberts is a business insights analyst on the Oncology team at Decision Resources Group.