Dr. Burstein on Pathological Complete Response

Harold J. Burstein, MD, PhD, Associate Professor of Medicine, Harvard Medical School, Medical Oncology/Solid Tumor Oncology, Dana-Farber Cancer Institute, discusses the use of pathological complete response (pCR) in the ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization) trials, which randomized patients into 3 different trial designs, each with 4 treatment arms that received lapatinib (Tykerb), trastuzumab (Herceptin), or both in the adjuvant and neoadjuvant setting.

Multiple studies have shown that pCR in the neoadjuvant setting indicates a better overall outcome in breast cancer patients. The use of pCR is not yet to the stage where it can be used as a surrogate endpoint for the approval of new drugs or to establish a new standard of care but it can work as a measurement of treatment efficacy. Despite the push towards its use, it has not translated into major gains in disease free survival (DFS), in prospective trials.

The pairing of the results from the NeoALTTO and the full ALTTO trial remains an important comparator for determining if pCR works as a predictive marker for disease free survival. The NeoALTO trial results were promising (Find out more) and demonstrated a great deal about pCR, if these findings are echoed in the rest of the ALTTO trial it will go a long way towards using this endpoint in future trials.

Other investigations suggest that pCR has no effect on outcomes for HER2-positive estrogen receptor (ER)-positive cancers suggesting that the ability of pCR to predict response is limited by ER status. The NeoALTTO trial demonstrated that the pCR rate was higher in patients with HER2-positive ER-negative than those that were ER-positive. It remains unclear if pCR is significant in ER-positive cancer, which comprises approximately 50% of HER2-positive cancers.