Leading breast cancer specialists recently shared insights on the optimal sequencing of antibody-drug conjugates (ADCs) in treating HER2-low metastatic breast cancer, highlighting key considerations for clinical decision-making.
Comparing ADC Options
The majority of clinicians expressed preference for trastuzumab deruxtecan (T-DXd) as the initial ADC choice, particularly noting its favorable toxicity profile and flexible dosing schedule. Dr. Misbah emphasized that "trastuzumab deruxtecan is very well tolerated with fewer adverse events than sacituzumab," highlighting the practical advantages of its every-three-week dosing regimen.
T-DXd's safety profile shows manageable adverse events, with grade 3 neutropenia occurring in 14% of patients. However, interstitial lung disease (ILD) remains a critical concern, with a 1% treatment-related mortality rate observed in the DESTINY-Breast-04 trial.
Managing Sacituzumab Govitecan
Sacituzumab govitecan demonstrates significant efficacy but requires careful management of side effects. About 50% of patients experience grade 3 or higher neutropenia, with 10% developing grade 3 diarrhea. Dr. Maiti noted the importance of proactive management: "I have tried using G-CSF for primary prophylaxis if insurance approves it. If not, dose reduction and secondary prophylaxis."
Treatment Sequencing Strategies
The expert panel addressed the crucial question of ADC sequencing. Dr. Kruse referenced recent data showing no significant difference in ADC response when including intervening chemotherapy. "It's hard to believe that any of the standard-of-care therapies are going to be better than either of the ADCs, so I just go back-to-back," she explained.
Special Population Considerations
Data from older adults (≥65 years) showed maintained efficacy with sacituzumab govitecan, with toxicity profiles similar to the general population. This finding provides reassurance for treating elderly patients with ADC therapy.
Future Directions
The ongoing ASCENT-07 trial investigating frontline sacituzumab govitecan is nearing completion of accrual. Dr. Sardesai expressed optimism: "I think we're going to see positive results based on moving it into earlier lines and better tolerability in that population that's not as heavily pretreated."
Clinical Practice Implications
For HR-positive, HER2-low patients, consensus favors T-DXd as the preferred initial ADC. However, some clinicians, like Dr. Bastola, prefer starting with sacituzumab govitecan in certain cases, particularly for patients with liver metastases, citing more extensive clinical data and concerns about ensuring patients receive both treatment options.
