While the results of these studies are particularly timely given the U.S. Food and Drug Administration’s revocation in November of its 2008 approval of bevacizumab in combination with paclitaxel for the treatment of metastatic breast cancer, they do little to quell the controversy surrounding bevacizumab, Dr. Alberto J. Montero and Dr. Charles Vogel said in an accompanying editorial.
The studies were designed based on the "plausible assumption" that a surrogate clinical end point such as progression-free survival – the end point used in the trials on which bevacizumab was initially approved – should be used in cases of metastatic breast cancer.
"The unresolved issue is whether significant improvements in a surrogate end point ... in the absence of a benefit for overall survival, are potentially predictive of curative benefits in patients with earlier-stage breast cancer," they said; only data on recurrence and survival from ongoing trials will resolve this issue (N. Engl. J. Med. 2012;366:374-5).
The controversy also involves broader questions about the use of surrogate end points, as well as about economic factors such as the ever-increasing cost of new cancer drugs.
"It is through this lens that the NSABP B-40 and GBG44 trials should be viewed, since each of these trials reports a significant improvement with bevacizumab in another putative surrogate clinical end point: pathological complete response," they said, adding that if such surrogate end points are ultimately shown to predict survival benefits in earlier-stage disease, their use in clinical research will be vindicated – and the FDA’s recent action will be further called into question.
"However, in the context of unsustainable expenditures for cancer care in the United States, any survival benefit of bevacizumab, or other molecularly targeted drugs, will be balanced against the considerable development costs of modern molecularly targeted oncology drugs," they said.
Dr. Montero and Dr. Vogel are with the University of Miami Sylvester Comprehensive Cancer Center. Dr. Vogel had several disclosures. The complete list is available with the full text of the editorial at NEJM.org.
