Since the HIV epidemic, the Food and Drug Administration has tried several different strategies to bring life-saving drugs to patients more quickly while preserving safety measures. In the cancer world, the need can be just as desperate, but drug development in this area has been hampered by low success rates. This is essentially due to inadequate laboratory models that do not reflect human biology very well and therefore are not very good at predicting what drugs will really make a positive impact cancer treatment. There is no shortage of potential drugs, but the cost required to test them in large clinical trials needed to gain approval forces drug companies to discard most of their drugs and hope they make the right “bet” on which ones move forward.
On Sept. 30, 2013, the FDA approved its first drug using the “neoadjuvant” model, which means drugs are being tested for their ability to shrink early-stage breast cancers prior to surgery. Since the disappearance of invasive cancer correlates with better long-term survival, the FDA proposed this new bar for accelerated approval of drugs as long as subsequent studies confirm their ability to delay or prevent recurrence.
The anti-HER2 antibody Perjeta, had already been approved for advanced HER2-positive breast cancer, when combined with the older antibody Herceptin plus chemotherapy. However, testing it in early-stage breast cancer requires much larger studies and time to determine if it can prevent or delay recurrence. Such studies have begun, but their final results are years away. Following this accelerated approval, Perjeta will now be available for patients with HER2-positive, early-stage breast cancer who are treated with neoadjuvant therapy. Trials are now assessing several new drugs in this fashion, such as the multi-center I-SPY 2 trial, testing a revolving list of targeted drugs with sophisticated tissue and imaging studies to also search for biomarkers that will tell us who will benefit the most.
There are pitfalls, however. Side effects are not as well-known in earlier phases of trials. The relationship between response in breast tumors and survival is quite complicated. The ultimate safeguard is close safety surveillance and parallel studies that look at both response and recurrence. The FDA will revoke drugs that do not eventually show an impact on recurrence, but it makes new drugs available much sooner albeit with less safety data. This is an important milestone in drug development and will significantly cut the time it takes to move drugs in a more curative setting. Hopefully, this is a trend that will be refined over time.
Debu Tripathy, MD
Editor-in-Chief, CURE Magazine