Neoadjuvant Systemic Therapy for Breast Cancer Searching for More Effectively Curative Therapies

Pathologic complete response (pCR) after neoadjuvant systemic therapy for localized breast cancer is associated with reduced risk of systemic recurrence. Compared with the traditional approach of empirically testing new agents in the adjuvant setting and waiting years for the results to be available, use of pCR as an intermediate pharmacodynamic biomarker offers the potential to accelerate testing of novel treatment approaches, and improve the probability of success in larger, more definitive trials with disease recurrence end points. Other advantages of aiming for higher pCR rates include the potential for less axillary surgery and higher breast conservation rates. The promise of this approach led the US Food and Drug Administration to accept pCR as an end point supporting accelerated regulatory approval of drugs in this setting. Randomized clinical trials have shown that systemic therapy has similar effects whether given before surgery as neoadjuvant therapy or after surgery as adjuvant therapy, providing additional support for this approach. Important caveats include the need for achieving large absolute improvements in pCR rates in order to translate into recurrence-free survival gains, and that full regulatory approval requires confirmation of improved event-free survival in the same trial showing improved pCR, or a separate confirmatory trial. This regulatory pathway has generated much interest in testing drugs in the neoadjuvant setting.

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