HER2-positive breast cancer patients who had a pathologic complete response had significantly better rates of event-free and overall survival compared with patients who did not have a pathologic complete response, according to results from the randomised, phase III Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO) trial presented at the 2013 San Antonio Breast Cancer Symposium.

Neoadjuvant therapy is treatment given to shrink or eliminate a tumour before surgery.

In some patients with breast cancer, neoadjuvant therapy effectively eliminates the tumour, and no invasive cancer is detectable in breast tissue and lymph nodes removed during surgery.

These patients are said to have had a pathologic complete response. “NeoALTTO is a randomised, phase III clinical trial evaluating whether a combination of two HER2-targeted therapies, trastuzumab and lapatinib, given with standard paclitaxel chemotherapy before surgery [neoadjuvant therapy] is better than just one of the HER2-targeted therapies given with the same chemotherapy in terms of inducing pathological complete responses,” said Martine Piccart-Gebhart, M.D., Ph.D., chair of the Breast International Group (BIG) in Brussels, Belgium.

“We previously reported that the combination therapy resulted in twice as many patients having a pathologic complete response. “Our new analysis shows that the improved pathologic complete response rates seen in the hormone receptor negative/HER2 positive subgroup seem to translate into better long-term outcomes for patients,” continued Piccart-Gebhart. “I believe that these results if confirmed in the large ALTTO adjuvant trial (to be reported at the 2014 ASCO meeting) will impact the process of drug development in the field of early HER2-positive breast cancer.”

From January 2008 to May 2010, Piccart-Gebhart and colleagues enrolled in the NeoALTTO study 455 patients with HER2-positive primary breast cancer with tumours greater than 2 cm in diameter. Of those patients, 154 were randomly assigned to lapatinib, 149 to trastuzumab, and 152 to the combination. These HER2-targeted therapies were given alone for six weeks and then the chemotherapy paclitaxel was also administered for a further 12 weeks, at which point surgery Results From NeoALTTO Trial Indicate Breast Cancer Patients Who Had Pathologic Complete Response Had Improved Event-free and Overall Survival Page 2 of 2 was conducted. After surgery, patients received adjuvant chemotherapy followed by the same HER2-targeted therapy as in the neoadjuvant phase to complete 52 weeks. “The NeoALTTO trial is indeed underpowered to make survival comparisons.

The results from NeoALTTO’s ‘sister’ trial, ALTTO [Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization], which is testing the effectiveness of dual treatment with trastuzumab and lapatinib after breast cancer surgery, will answer this when they become available in 2014. If the results of both studies are in line with each other, and depending on the strength of the ALTTO results, we could witness a new standard of care for managing primary HER2-positive breast cancer,” Piccart-Gebhart said.

The new data support the idea that pathological complete response is an acceptable surrogate endpoint. Indeed, after a median follow-up of about four years, patients who had a pathologic complete response were 62 percent more likely to have not experienced a cancer-related event such as cancer recurrence, cancer progression, development of a second cancer, and death, compared with patients who did not have a pathologic complete response. The overall risk of death was reduced by two thirds among patients who had a pathologic complete response.

Source: AACR