The FDA has recently released a draft 'Guidance to Industry', outlining a pathway to accelerate the approval for newer chemotherapy drugs to be used as neoadjuvant therapies and seeking public comments on the use of 'pathological complete response' as an end point for this approval.
Neoadjuvant treatment for cancer is the chemotherapy or radiotherapy that a patient receives before definitive treatment like surgery. The addition of a pretreatment to surgery often results in better outcomes and lowers the chances of recurrence of the cancer following surgery.
AdvertisementA new drug to treat breast cancer is first tried out in patients with metastatic disease i.e. cancer that has spread to other organs. It is available for patients with early-stage disease only after years of clinical trials. The drawback of this approach is that many patients miss the benefits of these new treatments. On the other hand, starting these drugs that have not undergone adequate clinical testing for safety may pose some risks in the form of side effects to the patient.
Taking the benefits and the possible disadvantages of using these chemotherapy drugs early, it has been suggested that these drugs could probably be tested first in those women with breast cancer who are more likely to have recurrence of the cancer following usual treatment. This includes women with high-grade tumors that are negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) (these cancers are referred to as triple negative).
For such newer drugs, the manufacturer should be able to demonstrate that treatment with the new drug has eradicated cancer to the point where there is no indication of cancer in the breast or lymph nodes; this is referred to as a 'pathologic complete response'. Researchers suggested that chemotherapy drugs likely to produce a pathologic complete response should be granted accelerated approval.
The new drug could be added to an existing regimen and its benefits when used with the current regimen can be first demonstrated. Continued follow up would provide efficacy and safety data over a prolonged duration. If the patient is disease free over this period, then full approval may be granted. If the manufacturer is unable to establish the benefit, the additional indication may be withdrawn.
This process of accelerated approval would benefit the numerous women who are at a risk of recurrence of breast cancer following breast cancer surgery.
Pathological Complete Response and Accelerated Drug Approval in Early Breast Cancer; Tatiana et al; N Engl J Med 2012; 366:2438-2441