RESEARCH RESULTS

Dr Janine Lombard is a medical oncology specialist at Calvary Mater in Newcastle and Breast Cancer Trials researcher, and has been involved in ALTTO for 18 years. She says the trial has not only greatly increased our understanding of ideal treatments for the roughly 20% of breast cancer tumours that over-express the HER2 (human epidermal growth factor receptor 2) protein, but it has also created a rich biobank of tumours.

“This is one of the biggest studies ever done in breast cancer and it was done across the entire world, so it has this absolutely unique collection of tumours,” Dr Lombard says. “It has helped advance a lot of understanding about HER2-positive breast cancers.”

Dr Lombard was the principal investigator in the ALTTO trial for Australia and New Zealand, where 223 women participated. “There was a good representation of Oceania, which at the time was often underrepresented in international studies.”

The latest publication from the trial was a 10-year comparison of 6,281 patients who had HER2-positive breast cancer. Too much HER2 protein is thought to cause cancer cells to grow and divide quicker.

“The study was designed with the premise that hopefully a combination of two drugs [trastuzumab and lapatinib] would improve outcomes,” Dr Lombard says. Because the two drugs work differently, it was hoped – based on previous evidence – that a combination would prevent the cancer from returning and possibly spreading to the brain. “However, the 10-year data supports an earlier publication that showed that was not to be the case,” she says.

Standard therapy is now trastuzamab alone, or in combination with another drug that has been developed since the study started, pertuzumab.

But far from being a ‘negative’ study, Dr Lombard says the ALTTO trial provides many grounds for optimism. “The thing we’ve understood in this decade and a half is that with treatment, outcomes for individuals with HER2-positive breast cancer are excellent,” she says. “Ten-year survival rates are close to 90% and that’s a huge improvement compared to before we had these anti-HER2 drugs. Because the survival rates are so good, it encourages us to think, as clinicians, ‘is there a group of women who we can give less chemotherapy to?’”

Dr Lombard says the breast cancer treatment landscape has changed a lot since the ALTTO trial started. Along with the development of next-generation drugs, treatment protocols now often recommend chemotherapy before surgery, whereas all the patients in the trial had surgery before chemotherapy.

Publication

Final analysis of the ALTTO trial: adjuvant trastuzumab in sequence or in combination with lapatinib in patients with HER2-positive early breast cancer [BIG 2-06/NCCTG N063D (Alliance)] de Azambuja, E. et al. ESMO Open, Volume 9, Issue 11, 103938. https://doi.org/10.1016/j.esmoop.2024.103938