Can we save money by spending more? A case for cancer research

“You can’t always get what you want, but if you try sometimes, you just might find, you get what you need.”

– M. Jagger/K. Richards

As a nation, we are actively discussing ways to reduce health care costs while enhancing the quality of care we give and receive. Vitriolic town hall meetings, reports of decreasing confidence in the president’s ability to “fix” the problem, squabbling between the House and the Senate, and ongoing debates about the value of a “public option” have occupied much of the news.

As cancer care specialists, we know that we are contributing to rising health care costs. Cytotoxic chemotherapy, mostly directed at DNA synthesis, is effective; broader use of these modalities in the adjuvant setting has driven down the death rate from some cancers. The increasing use of adjuvant therapy for cancer by itself is expensive without even considering the use of antiemetics, hematopoietic growth factors and charges for infusions. Even as we treat more patients with these cytotoxic therapies, we know this approach remains insufficient for many cancers.

Douglas Yee

Investments in basic and population science have identified new targets for cancer treatment; this strategy has paid off for our patients. We’ve seen the subsequent development of many new drugs directed at new molecular targets. FDA approval of new drugs in previously refractory diseases, such as hepatocellular carcinoma and glioblastoma, has increased treatment options. Common diseases such as breast cancer have also benefited from discoveries that led to new therapies (trastuzumab, bevacizumab, nanoparticle albumin-bound paclitaxel). These treatments are effective and expensive.

But now that we have these drugs, do we really know how to use them? Do we know which tumors are most susceptible to which agents? Do we know how to use drugs in combination or in sequence? For some drugs, such as antiangiogenic agents, do we know how long to continue using them? Are there additional pathways that need targeting?

How to get answers

I would submit that all of these questions are research questions. Furthermore, these questions can be answered by considering every cancer patient a research subject. When I say “research subject,” most people think “clinical trial.” It is clear that enrollment of patients on randomized clinical trials has led to improvements in cancer outcomes and continued participation by our patients can answer these key questions in the future.

As recently featured in The New York Times on Aug. 3 (Forty Years’ War, Lack of Study Volunteers May Hobble Cancer Fight) the low accrual of patients on clinical trials slows advances in care. Although there are many barriers to enrollment on studies, we must engage our patients in the value of this process. We are asking a lot of our patients: more tests, more visits, potentially more aggressive unproven therapy.

For example, the clinical trial known as I-SPY2 is an adaptive phase-2 clinical trial that will evaluate targeted therapies in women with locally advanced breast cancer. Laura Esserman, MD, has led the development of the trial, and I believe this trial will advance new therapies, genomic and proteomic predictive biomarkers, and investigative imaging with the long-term goal of improving breast cancer outcomes by targeting specific molecular phenotypes with the appropriate drug. This trial requires a lot from women; investigational biopsies, multiple breast MRIs, and exposure to novel, but unproven, targeted therapies. This trial is scheduled to open soon. Disclaimer: I’ve been involved with the planning of this trial — and I believe this trial will result in getting the right drug to the right patient.

Even if we are successful in increasing the number of patients on randomized clinical trials, it is still highly likely that most patients will be treated “off-study.” However, these patients can still be considered research subjects if we could maintain a database of detailed clinical records and tissue specimens. Understanding practice patterns, outcomes and costs can all be derived from well-curated and well-maintained databases. When these types of databases are linked to tissue specimens, substantial advances can be made.

At my first faculty job, at the University of Texas Health Sciences Center at San Antonio, the late William L. McGuire created such a database linked to frozen breast cancer specimens. These samples were obtained to measure steroid hormone receptor levels, but detailed clinical outcomes were maintained for years after the collection ended. This frozen tumor bank was subsequently used to show the prognostic implication of HER2 gene amplification.

Understanding that HER2 gene amplification is a poor prognostic factor led to the idea that this pathway could be inhibited. Subsequent development of trastuzumab (Herceptin, Genentech) proved that molecular targeting of genetic aberrations had substantial clinical impact. Of course, when Dr. McGuire began collecting these specimens he had no idea that he was going to study HER2, but the well-maintained clinical database connected to the specimens proved their worth. Of course, these specimens were collected in a “pre-HIPAA” era and clinical records were reviewed without explicit patient consent. Nonetheless, I think the value of this database and tumor bank cannot be underestimated, yet I do not believe the women who contributed tumors to this bank were compromised in any way.

Potential solutions

So how can we save money by spending more? I will be the first to admit that I’m not a health economist, but I propose these measures as common sense solutions dictated by our past history.

A federal public option for cancer care would pay all health care costs for patients enrolled on a clinical trial. We are asking a lot from patients when we ask them to enroll on a clinical trial, so why not “pick up the tab?” I would suggest that this solution would have numerous benefits: the disappearance of insurance company wrangling about “research study costs,” enhanced interest from hospitals and physicians to offer clinical trials to more patients, more motivated patients now incentivized to participate in studies, and enhanced evidenced-based care.

Of course a governing body composed of interested parties (advocates, regulatory agencies, investigators, pharmaceutical companies, etc.) would need to prioritize the type of trial to be performed, but this is exactly what has happened with the I-SPY2 study. It would be feasible to prioritize, design and conduct high-impact cancer prevention, treatment and survivorship studies if there were clear methods of paying for the trials and their associated costs. Moreover, we could begin to perform the complex predictive biomarker studies necessary to optimize cancer treatment. In my experience, the current sources of funding for clinical trials (either federal or industrial) are loathe to add these “extra” costs into their trial design.

Of course we already pay for cancer treatment in federally funded health care programs (Medicare/Medicaid). In my ideal world, private insurance companies would contribute to this public option because this investment would eventually result in providing the best evidenced-based care in a cost-effective way. In essence, I propose we use the dollars we already spend on cancer care to support clinical trials; we will be providing optimal care for our patients and advancing the field.

Federal, state and private funding would support clinical databases. With the advent of electronic medical records, is there any reason not to create these linked databases? I believe we already have a wealth of data that could be used to inform medical practice. Understanding patterns of practice and outcomes could help us define optimal care practices that might be difficult to define in randomized trials. By linking these clinical results to tissue samples, we could speed the development of predictive biomarkers; even after drugs are already marketed.

For example, in breast cancer, we are debating the value of anthracyclines vs. taxanes. The randomized clinical trials have suggested these two classes of drugs are both good, and taxanes may have a slight edge, leading to the argument that anthracyclines are no longer needed. To me, this debate is misguided. We have all seen patients treated in the neoadjuvant setting that benefit from anthracyclines and do not benefit from taxanes and vice versa. In my opinion, developing biomarkers to predict response and toxicity to specific drugs is a high priority. Even if only a minority of patients needs an anthracycline, we should understand who they are.

There are hundreds of thousands of women who have previously been treated in the adjuvant setting who could help answer this question. Advances in obtaining DNA, RNA and protein from formalin-fixed paraffin embedded tissues increase the value of tissue specimens already obtained and sitting in pathology departments across the country. Of course many groups, including private insurers and health plans, are already collecting this information. I propose we provide additional funding resources to capture as many patients as possible into this database and make these resources available to investigators. Obviously, issues regarding privacy, consent and use of data would need to be resolved, but I believe that most patients would be willing to contribute to advancing cancer research.

We’ve already spent billions of taxpayer dollars on cancer research and care. We’ve seen some remarkable advances in our understanding of the disease and some of that knowledge has paid off on improved cancer therapies. Further spending on clinical trials and database creation fits the mandate of supporting “comparative effectiveness research.” In order to complete our mission, I believe the time is right to spend more. We need to get our patients what they need.

For more information:

• Barker AD. Clin Pharmacol Ther. 2009;86:97-100.
• Slamon DJ. Science. 1987;235:177-182.