I think that any statement about major advances in cancer care ought to be comprehensive and carefully considered. I find it particularly useful to reflect on what we mean when we call something an "advance." Here are some categories that I used to sort out different kinds of advances.
- Category A: Advances where some new, proof-of-principle in science was demonstrated; a breakthrough in scientific terms.
- Category B: Advances that have major impact on lives or patterns of care, either due to the large number of affected patients or the large magnitude of change in the outcome or pattern of care.
- Category C: Advances that are generally encouraging signs of progress. This is where most of the advances would be categorized, in my opinion. These are findings affecting fewer patients, influencing fewer life-years or producing generally less dramatic changes. Some of these advances are of greater interest to the lay population because of business implications or because they address topics of broad interest or shared experience.
Examples of Category A advances include the work with PARP inhibitors for selected patients with breast cancer in 2009, and the work with the new oral ALK inhibitor
(crizotinib) for lung cancer patients in 2010 . These represent a new category of treatment for a subset of patients with common diseases.
Previously, when the first breakthrough targeted therapy came along in the form of Imatinib (Gleevec), it was a story of major impact in rare diseases like chronic myelogenous leukemia (CML) or gastrointestinal stromal tumor (GIST). In 2010, the new rare disease breakthroughs include vandetanib, an oral targeted agent for metastatic medullary thyroid cancer and everolimus, recently shown to dramatically improve progression free survival for pancreatic neuroendocrine tumors
. When we're talking about a small subset of common diseases, it creates a new dilemma -- how do we screen all of these patients with common diseases to find the subsets of patients who would dramatically benefit from specific targeted therapy? It will take a lot of money, technology, and infrastructure change to accommodate the personalized cancer care approach. It is fascinating, exciting, and still daunting.
On the more positive side in Category B was the finding that the early integration of palliative care in patients with advanced lung cancer
was associated with not only improved quality of life and decreased intensity of common symptoms, but also an increase in survival of 2.7 months. This is the magnitude of survival benefit that is similar to that seen when chemotherapy was compared to not using chemotherapy. It was also demonstrated recently that physician-patient communication towards the end of life was associated with patient choices that lead to improved end-of-life care quality and value
Some of the Category B level "advances" represent disappointing, albeit important news. For example, the findings from the SELECT trial reported in December of 2008 demonstrated that vitamin E and selenium do not prevent prostate cancer
. Similarly, we found 3 months later, in March of 2009, that PSA screening does not
effectively save lives in the way that we had hoped.
Finally, we learned in 2009 that the expensive monoclonal antibody, bevacizumab, while effective as part of the regimen treating advanced colon cancer, is not actually useful as part of a strategy to prevent recurrence of colon cancer once it's been removed. Furthermore, in June of 2010 (also at the ASCO annual meeting) we found out that there is no benefit to adding cetuximab, a different monoclonal antibody therapy, with this same goal of preventing recurrent disease. Ironically, the feelings about that news was somewhat mixed for oncologists. On one hand, oncologists always want to see positive findings about new therapies, but some oncologists also noted that the overall health care expense associated with a positive finding on these particular studies may have created some real dilemmas.
So what needs to be done to create a world in which more category A and B (high impact) findings are produced, where the bulk of the advances are no longer stacked up in Category C (lower impact)? The cancer research world needs a better engine and more fuel, and that's where organizations like ASCO are perfectly on target with their recommendations.
The "engine" is the clinical research infrastructure, and it's an old and inefficient engine that needs to be fundamentally reformed according to a report of the Institute of Medicine
issued in April of this year. The "fuel" is the funding, and fuel is necessary for any engine to run. With expected large increases in the relative impact of cancer on the nation and its health and finances, the time for fueling up a fixed engine is now upon us.