Discussion
death, tumors, TTP, aggressive disease
BRAIN METASTASES, DISEASE, TTP, TUMORS
Trastuzumab continues to be the backbone of therapy in the first-line setting for management of HER2+ MBC. When given in combination with a second anti-HER2-directed agent, pertuzumab, a considerable 18.5-month progression-free survival (PFS) is achieved, as observed in CLEOPATRA.To our knowledge, this study provides the longest follow-up on trastuzumab when utilized in the metastatic setting and is the first to identify and clinically characterize a cohort of survivors after 2 decades. Use of TCH for women with HER2+ MBC resulted in a 10% OS with median OS of 39.78 months, median TTP of 10.78 months, and a PR and CRR of 72.5% and 42.5%, respectively. In terms of response follow-up to dual HER2-blockade, the end-of-study results from CLEOPATRA reported a median OS of 57.1 months in contrast to the 40.8 months of median OS in the placebo arm (trastuzumab/docetaxel alone) (HR 0.69; 95% CI, 0.58-0.82). The updated 8-year follow-up results showed a 37% OS in contrast to a 23% OS achieved in the placebo arm.In a 5-year follow-up study of trastuzumab in combination with pertuzumab and paclitaxel, 86% of participants achieved a 6-month PFS, with a median of 24.2 months.AE at long-term follow-up were similar to those previously reported and are, therefore, not discussed in detail.Our study contains limitations that are acknowledged. Cause of death was not attributed to a specific cause in 42% of participants, as this data were not available. As a result, conclusions regarding cancer-specific mortality could not be drawn. To our knowledge, patients did not receive any additional targeted therapies other than Herceptin.Within our cohorts, all patients had an aggressive disease course marked by the presence of stage IV disease on enrollment. Remarkably, the presence of visceral and even brain metastases did not lead to a poorer outcome in some patients, pointing out the need for enhanced characterization of tumors that might be highly sensitive to HER2 inhibition. Identification of additional genomic biomarkers associated with long-term survival may guide therapy individualization to allow more aggressive management of patients anticipated to respond poorly to standard of care therapies. Conversely, enhanced understanding of patients achieving durable responses to therapy may aid in de-escalation approaches. Further follow-up from recent phase II and phase III clinical trials are awaited.