Cancer researchers who nourish ideas to fruition must start focusing on the clinical values of their discoveries and not just whether their ideas work, several experts said at a Special Session of the American Association of Cancer Research (AACR) Annual Meeting, held April 17-21 in Washington, DC.

Change in Cost vs Survival

Between 1995 and 2007, "the cost of new prescription drugs for breast and colorectal cancer in clinical trials increased over 100 times, but the overall survival improvement in the new arm has stayed at less than 1%," Thomas J. Smith, MD, Professor of Medicine and Palliative Care Research at the Massey Cancer Center, Virginia Commonwealth University Health System, told the AACR ­audience.

Tito Fojo, MD, PhD, of the National Cancer Institute pointed to drugs like cetuximab (Erbitux), which can add $70,000 to patient medical costs but improve survival for only 1 month to 6 weeks, often at an additional cost of serious side effects. He also noted that adding bevacizumab (Avastin) to breast cancer treatment "improves progression-free survival but has yet to be shown to confer a significant survival advantage."

Dr. Fojo stressed that drug costs are only one part of the problem, noting that of equal concern is the possibility that the increasingly marginal benefits seen in clinical trials are in fact masking harmful effects in some patients. As an example, he cited the negative impact of cetuximab on progression-free survival when it is given to patients with colorectal cancer whose tumors harbor a KRAS mutation.¹ In addition, he expressed concern that overall survival in some patients with breast cancer may be adversely impacted by single-nucleotide polymorphisms (SNPs) in the promoter region of the vascular endothelial growth factor (VEGF) receptor.^2,3

Dr. Fojo concluded his presentation by urging audience members-many of whom were investigators involved in basic research-to work to identify markers that predict response or the potential for harm before drugs reach clinical trials.

10 Cost-control Measures

Dr. Smith, an oncologist, proposed "10 steps to bend the cancer cost curve." He stated that the current double-digit rate of growth is simply not sustainable. The cost of insurance for a family of four has doubled from $6,000 to $12,000 in just 8 years, and continuation will have the consequence of fewer "haves" with coverage for anything, and many more "have-nots" without coverage for even the basics of curative and adjuvant care. Here are some of the points Dr. Smith made:

• "Expand use of biologic imaging (PET-CT), tumor markers, or circulating tumor cells to limit duration of ineffective therapies. At the same time, limit the use of ineffective tests such as blood tumor markers and CAT, PET, or bone scans in surveillance of breast cancer."
• "For many cancer types, use sequential monotherapy for metastatic disease." This approach results in less toxicity and is also less costly.
• "Provide tools to care providers to reset the patient's unrealistic expectations of benefit" by discussing advance directives, prognosis, life planning, legacy, and legal issues, and by obtaining "truly informed consent." Patients need answers to the question, "How long will I live with or without chemo, and what will that time be like?"

A Different Take

But David R. Parkinson, MD, of Nodality, South San Francisco, has a different take on the dilemmas facing cancer researchers, providers, and patients. Dr. Parkinson believes that many of the inefficiencies in the system stem from a disconnect between the way we characterize patients and drug treatments. He maintains that truly personalized medicine, where biomarkers allow for targeted therapies that work on the patient's particular malignancy, is the "missing piece for rational, efficient treatment." Right now, he says, "we don't have the tools for biologic management of patients."

But technologies are emerging that Dr. Parkinson believes will allow for the development of biologic tools so that clinical decisions can be based on individual biology. Rational, efficient treatment must be built on a "three-legged stool," he said-better understanding of the biology of malignancy; development of targeted therapies; and creation of tools for biologic management of patients.

References

1. Allegra CJ, Jessup JM, Somerfield MR, et al: American Society of Clinical Oncology Provisional Clinical Opinion: Testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol 27:2091-2096, 2009.

2. Schneider BP, Wang M, Radovich M, et al: Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol 26:4672-4678, 2008.

3. Gray R, Bhattacharya S, Bowden C, et al: Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer. J Clin Oncol 27:4966-4972, 2009.