Prognostic impact of the choice of chemotherapy after first-line CDK4/6 inhibitor therapy in patients with metastatic hormone receptor-positive, HER2-negative breast cancer

Abstract

Introduction: Whereas CDK4/6 inhibitors (CDK4/6i) are the standard first-line therapy for patients with hormone receptor-positive (HRpos), HER2-negative (HER2neg) metastatic breast cancer, guidelines on treatment options after progression on CDK4/6i are more diverse. Chemotherapy is recommended if a patient develops endocrine resistance or experiences a visceral crisis. However, the impact of the choice of chemotherapy remains unknown. Methods: HRpos/HER2neg patients who received first-line CDK4/6i, followed by second-line chemotherapy (N =215) were selected from the prospective PRAEGNANT registry (NCT02338167). Cox regression analyses were used to evaluate the correlation between the choice of chemotherapy (capecitabine monotherapy, cape citabine +bevacizumab, taxane monotherapy, taxane +bevacizumab, anthracycline, other chemotherapeutics) and progression-free survival (PFS) and overall survival (OS). Results: Patients who received second-line chemotherapy mostly had high-grade tumors (G2: 62.3 %, G3: 33.3 %), visceral metastases (62.3 %) and developed metastatic disease following a primary breast cancer diagnosis (73.8 %). Capecitabine was the most common regimen (25.1 %), followed by taxane +bevacizumab (17.2 %). When adjusting for other prognostic factors (age, BMI, grading, ECOG, metastasis group and time to metastases), the choice of chemotherapy did not influence PFS (p =0.16) nor OS (p =0.47). Adjusted hazard ratios for PFS were lowest in regimens with bevacizumab (capecitabine as reference; capecitabine +bev acizumab: 0.53 (95 %CI: 0.29, 0.97); taxane +bevacizumab: 0.64 (95 %CI 0.35, 1.15)). Conclusion: Although the choice of chemotherapy post-CDK4/6i did not significantly affect PFS or OS, combi nations with bevacizumab may have some benefit. Nevertheless, considering side effects may be most important when choosing the type of second-line chemotherapy.