Long-term survival of de novo stage IV human epidermal growth factor receptor 2 (HER2)-positive breast cancers treated with HER2 targeted therapy.

Abstract

1021 Background: An increasing number of metastatic HER2 positive cancers represent de novo stage IV disease as fewer early stage patients relapse. We hypothesize that a subset of these has long progression free survival (PFS) after initial combined modality HER2-targeted therapies. Methods: 483 patients with de novo stage IV HER2 positive breast cancer diagnosed between 1998-2015 were identified through the medical records at Yale and MD Anderson Cancer Centers, respectively. Treatment, clinical variables and survival were extracted and compared between those who achieved “no evidence of disease” (NED) status with initial therapy and those who did not. Results: All patients received trastuzumab and 94 (20%) also received pertuzumab as first line therapy.The median OS was 5.5 years (95% Cl: 4.8-6.2); OS rates at 5 and 10 years were 54% (95% CI: 48%-60.4%) and 18% (95% Cl: 11.4%-28.3%), respectively and PFS were 41% (95% CI: 35%-48%) and 41% (95% CI: 35%-48%). Sixty-three patients (13.0%; 95% CI: 10.2% -16.4%) achieved NED. The PFS and OS at 5 and 10 years were the same 100% and 98% (95% CI: 94.6%-100%), respectively. For patients with no-NED (n = 420), the median OS was 4.7 years (95% Cl: 4.2-5.3), the PFS and OS rates at 5 and 10 years were 12% (95% CI: 4.5%-30.4%) and 0% and 45% (95% CI: 38.4%-52.0%) and 4% (95% CI: 1.3%-13.2%), respectively. NED patients had significantly longer progression free survival (log-rank test p≤0.001) and overall survival (log-rank test p≤0.001), more frequently had single organ site metastasis (76% vs 57%, p = 0.005), and more frequently had surgery for primary tumor (59% vs. 25%, p ≤0.001) than no-NED patients, but there was no significant difference in age, grade, race, year of diagnosis, ER status, treatment distribution, or radiation between the groups. Conclusions: About 13% of de novo, stage IV, HER-2 positive MBC patients achieved NED with HER-2 targeted therapies, all of these patients were progression free at 5 years and overall survival at 10-years was 98% compared to 4% among those with no-NED in our data sets. These results suggest that aggressive multimodality therapy of newly diagnosed stage IV HER2 positive cancers to render them NED may be warranted.