What this trial does suggest is that women with premenopausal HR-positive breast cancer have options. Specifically, women who cannot tolerate Tam or have a contraindication can safely and effectively be treated with AIs plus OFS. The inconvenience of monthly injections was not addressed in this initial presentation, but could potentially decrease patients’ reported quality of life. We await additional results of the SOFT trial later this year.
The ALTTO Trial
The second plenary abstract presented was the ALTTO trial, which sought to evaluate the role of dual anti-HER2 therapy in the adjuvant setting. Trastuzumab (T) has been standard of care in the treatment of HER2-positive breast cancer since 2005. In recent years, dual-HER2 blockade has attracted research and clinical interest: pertuzumab plus T with chemotherapy improves overall survival compared with T plus chemotherapy for metastatic breast cancer, and pertuzumab or lapatinib (L) added to T plus chemotherapy increases pathologic complete response in the neoadjuvant setting compared with T plus chemotherapy alone. ALTTO is the first study to evaluate whether dual HER2 blockade in the adjuvant setting can improve outcomes.
ALTTO was a phase 3, international trial that randomly assigned patients with HER2-positive early-stage breast cancer to one of four treatment arms: (L+T), T followed by L (TàL), L alone, or T alone. Anti-HER2 therapy was initiated sequentially after chemotherapy or concurrently. The L-alone arm was closed in August 2011 for futility and was not included in the presentation. As with the SOFT/TEXT trials and other adjuvant trials in early-stage breast cancer, the event rate was lower than expected. After a median follow-up of 4.5 years, there was no difference in DFS between L+T compared with T alone or TàL compared with T alone. There were more instances of diarrhea, rash, and hepatobiliary adverse events in the lapatinib-containing arms, but there was no difference in cardiac toxicity, which was infrequent overall. The lack of added benefit with the addition of lapatinib to trastuzumab-containing chemotherapy regimens was surprising in light of the doubling of pathologic complete response rate observed when lapatinib was added to trastuzumab in the neoALTTO trial.
The negative results from ALTTO raise questions about clinical trial design in breast cancer; given the low number of events seen in early-stage breast cancer, large, expensive trials are required. It is clear that breast cancer trials need to include high-risk patients in order to see more events and have adequate statistical power, but low-risk patients constitute a large proportion of patients with breast cancer, and are only low risk until they recur. Biomarker and other correlative studies are ongoing and may hopefully shed light on a subpopulation that could benefit from adjuvant lapatinib.
Jennifer Matro, MD, is Chief Fellow of Medical Oncology and Hematology at Fox Chase Cancer Center and Temple University Hospital.