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NeoALTTO Trial: Final Analysis Examines Neoadjuvant Lapatinib/Trastuzumab in HER2-Positive Breast Cancer


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Final analysis of results from a randomized clinical trial of lapatinib and trastuzumab given before surgery in patients with early HER2-positive breast cancer has found that women who had a pathologic complete response survived longer without cancer recurrence than patients who did not. This was more likely to happen in patients who received the two anticancer drugs together, rather than as single agents. Long-term findings from the NeoALTTO trial were presented by Paolo Nuciforo, MD, PhD, at the 12th European Breast Cancer Conference (Abstract 23).

Dr. Nuciforo, principal investigator at Vall d'Hebron Institute of Oncology, Barcelona, presented results from nearly 10 years of follow-up from the international NeoALTTO BIG-06 trial, in which patients were randomly assigned to receive either trastuzumab or lapatinib alone or in combination.

Paolo Nuciforo, MD, PhD

Paolo Nuciforo, MD, PhD

He said, “Patients who achieved a pathologic complete response had significantly better long-term survival compared to those who did not achieve pathologic complete response. Although overall survival rates did not differ significantly between the three treatment groups, nearly twice as many patients achieved pathologic complete response if they received both drugs, 51% compared to 27.1% of patients receiving only one drug in the other two arms of the study combined.”

Study Methods and Long-Term Follow-up

NeoALTTO BIG-06 enrolled 455 women with early HER2-positive cancer to receive either neoadjuvant trastuzumab or lapatinib alone or in combination. After surgery, the patients were given three cycles of chemotherapy followed by 34 weeks of whichever therapy they had originally been assigned to receive.

With a median of 9.7 years of follow-up, event-free survival was seen in 69% of patients receiving both drugs, 65% of the trastuzumab-only group, and 63% of the lapatinib-only group. These differences were not statistically significant. Overall survival rates were 80% in the combination group, 77% in the lapatinib group, and 76% in the trastuzumab group, with no statistically significant differences between the groups.

When the researchers compared women who had achieved pathologic complete response with those who had not in all three treatment groups, they found that event-free survival and overall survival were significantly better in women who had a pathologic complete response; 77% of patients who had a pathologic complete response survived 9 years event-free compared to 61% of patients who did not have pathologic complete response. Moreover, 88% of patients with a pathologic complete response were still alive at 9 years compared to 72% of patients who did not have pathologic complete response. Subgroup analysis showed that these associations were statistically significant in women who received the drug combination or whose disease was hormone receptor–negative.

Dr. Nuciforo said, “Although we might have expected a significantly higher overall survival in the group of women receiving the combination of lapatinib and trastuzumab where pathologic complete response rates were higher, this was not the case. This was possibly due to the fact that the study was not powered to detect small differences in survival between the three groups.”

"Patients who achieved a pathologic complete response had significantly better long-term survival compared to those who did not achieve pathologic complete response. Although overall survival rates did not differ significantly between the three treatment groups, nearly twice as many patients achieved pathologic complete response if they received both drugs."
— Paolo Nuciforo, MD, PhD

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“The results from this analysis show that patients who achieve pathologic complete response are significantly more likely to survive for longer than those who do not achieve pathologic complete response. This validates pathologic complete response as an early indicator of long-term outcome for HER2-positive disease and could help doctors decide on the best treatment. On one hand, patients not achieving a pathologic complete response may be at higher risk of recurrence, and giving extended therapy to them could potentially lower this risk. On the other hand, those patients who do achieve pathologic complete response could be spared additional toxic treatments,” he continued.

“At present, all women with HER2-positive breast cancer receive toxic adjuvant chemotherapy after anti-HER2 neoadjuvant treatment to reduce the risk of recurrence after surgery. However, not all women have the same risk. If we could predict, for example with pathologic complete response, which patients are at high risk of their cancer recurring in 3, 5, or 10 years, we could give more aggressive adjuvant therapies only to these women and not to those women who have achieved pathologic complete response and are at low risk of recurrence,” Dr. Nuciforo concluded.

The study authors wrote, “Long-term follow-up analysis confirms that patients with pathologic complete response have a significant higher survival probability than those who did not achieve pathologic complete response, supporting pathologic complete response as an early indicator of long-term outcome in HER2-positive disease. These effects were particularly seen in patients with negative hormone receptors and dual anti-HER2 treatment. Although overall survival rates were not significantly different between arms, patients who reached pathologic complete response with lapatinib plus trastuzumab therapy were nearly doubled compared to the patients in the single agent arms.”

Disclosure: For full disclosures of the study authors, visit cm.eortc.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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