ALTTO and NeoALTTO studies presented updated results at the ASCO Annual Meeting in Chicago
ASCO ANNUAL MEETING – June 2-6, 2017 (Chicago, USA)
On 4 and 5 June 2017, both the ALTTO and NeoALTTO studies presented updated results at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.
ALTTO is a randomised trial comparing adjuvant (post-surgery) lapatinib with trastuzumab, given either alone, combined or sequentially, in patients with HER2-positive early breast cancer. The main aim of the study was to see whether treating this type of breast cancer with the two drugs trying to block HER2 (dual therapy or dual “blockade”) would be better than one. This international study, originally sponsored by GSK but now transferred to Novartis, involved over 8,300 patients from 44 countries. Now that all patients have been followed for at least 5 years, Dr. Alvaro Moreno-Aspitia (Hematologist & Oncologist, Mayo Clinic, Jacksonville, Florida) presented the updated results.
The analysis looked at the participating patients’ chances of being free of cancer (disease-free survival or DFS) 5 years after being given a specific treatment. As such, DFS is a measure of treatment effectiveness. For the group of patients treated with lapatinib and trastuzumab combined, DFS was 85% compared with 82% in the group of patients treated with trastuzumab alone (hazard ratio [HR] of 0.86 [95% CI 0.74-1.00]). The group of patients that was first treated with trastuzumab followed by lapatinib had a DFS of 84% (HR of 0.93 [95% CI 0.81-108]) compared to a DFS of 82% for those treated with trastuzumab alone. Although the DFS percentages were higher for the combination and sequential treatments than for trastuzumab alone, these differences were not statistically significant, and so the study’s main results remain unchanged: the evidence generated does not support adding lapatinib to trastuzumab as the standard of care for patients with HER-2 positive early breast cancer.
The difference in DFS between trastuzumab combined with lapatinib compared with trastuzumab alone was slightly higher, though not statistically significant, in the group of patients with hormone receptor negative disease (84% versus 80%), and thus may be an interesting area for further exploration. The occurrence of adverse events was higher in the trastuzumab combined with lapatinib group (93%) compared with the trastuzumab alone group (64%). Overall, this 5-year analysis showed results to those of the primary analysis presented in 2014.
NeoALTTO is a randomised clinical trial comparing lapatinib with trastuzumab in 454 patients with HER2-positive breast cancer in the neoadjuvant (pre-surgical) setting. The primary analysis of this study, published in 2012, showed that dual HER2-targeted therapy with lapatinib and trastuzumab resulted in more patients achieving a pathological complete response (pCR), meaning a disappearance of all visible signs of cancer, compared to a single HER2-targeted therapy (trastuzumab).
During a poster discussion, Dr. Jens Huober (Department of Gynaecology and Obstetrics, Ulm University Hospital, Germany) presented an updated analysis of NeoALTTO, when patients had been followed for a median period of 6.7 years. The 6-year event free survival (EFS) (no signs of breast cancer returning) and overall survival (OS) were not significantly different between the two types of treatment, although the combination of trastuzumab with lapatinib showed numerically higher EFS compared to trastuzumab alone (74% vs 67%), especially in patients with hormone receptor negative disease (74% vs 63%). In addition, this analysis showed that patients who achieved a pCR had a significantly higher 6-year EFS and OS compared to those without pCR.
Follow-up for both studies will continue for at least ten years after enrolment. Exploratory (translational) research using the biological samples and data from these studies is ongoing.