Clinico-pathological predictors of radiologic complete response to first-line anti-HER2 therapy in metastatic breast cancer: insights from real-world data of a nationwide cohort

Abstract

Background: Up to 6-8% of patients with HER2 positive metastatic breast cancer (MBC) experience a radiologic complete response (rCR) to a first line of therapy, but these results mostly derive from dated and/or limited cohorts. Currently, there is limited data regarding which variables could predictive of a rCR to anti-HER2 therapies. Methods: Patients were selected from the database of the GIM14 study (NCT02284581) and classified according to the best radiologic response obtained to the first line anti-HER2 therapy and upon time-to-treatment-discontinuation (TTD). rCR was defined as complete response (CR) with a TTD > 3 months. The association across variables was tested through logistic regression and their prognostic impact in terms of overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Results: Of the 3,423 patients included in the GIM14 study, 814 had HER2 positive MBC and data about best radiological response were available for 545 patients. Eighty patients (14.7%) experienced a rCR to first line anti-HER2 therapy with a TTD > 3 months. At multivariable analysis, HER2 Immunohistochemistry score 3+ (OR 2.03, p-value=0.01), presence of non visceral metastases (OR 1.51, p-value=0.01) and 1 metastatic site (OR 2.49, p-value= 0.01) were significantly associated with higher odds of obtaining a CR. Furthermore, amongst the 80 patients achieving a rCR, 56 (73%) experienced a durable and sustained CR with a TTD > 18 months. At multivariable analysis, only type of anti-HER2 therapy (OR 0.13 p-value<0.01 for trastuzumab-based therapy and OR 0.08, p-value=0.04 for other anti-HER2 therapy) was associated with a higher probability of achieving a CR with a TTD > 18 months. A median OS of 10.22 years was observed for patients that had achieved a CR to a first line anti-HER2 therapy and a TTD > 3 months. For patients with a CR and TTD > 18 months, a median OS of 12.73 years was observed. Conclusions: This study characterized a real-world cohort of HER2 positive MBC patients experiencing radiologic complete response to a first line treatment. Higher odds of achieving a complete response to a first-line anti-HER2 therapy with a TTD > 3 months were observed for HER2 Immunohistochemistry score 3+, presence of visceral metastases and presence of a single metastatic site. Additionally, a sustained complete response with a TTD > 18 months, was described in a subset of patients that had been exposed to a trastuzumab-based therapy.