Second-line treatment strategy following CDK4/6 inhibitors for HR-positive and HER2-negative metastatic breast cancer patients: a multicentric, retrospective, observational study.

PURPOSE: The standard first-line treatment for patients with hormone receptor-positive (HR +) human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer is cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy (ET). Optimal therapy after CDK4/6 inhibitors remains to be determined. We aimed to define the appropriate second-line treatment after CDK4/6 inhibitors in a real-life population.

METHODS: Patients who had received CDK4/6 inhibitors with aromatase inhibitors (AIs) for HR + /HER2- metastatic breast cancer were included from March 2017 to May 2021 at five French cancer centers.The primary objective was to describe second-line treatment after primary treatment with CDK4/6 inhibitors plus AIs.

RESULTS: We included 381 patients who received CDK4/6 inhibitors combined with AIs as first-line therapy. Patients with progressive disease (N = 165) benefited from a second-line of treatment: 69 (41.8%) were treated with chemotherapy, while 90 (54.6%) received endocrine therapy (ET alone: 59, 35.8%; ET plus targeted therapy: 31, 18.8%).Patients on chemotherapy were younger compared to those receiving ET (p = 0.011). Patients experiencing earlier progression were more likely to benefit from chemotherapy than ET (p = 0.001). Patients with visceral disease at diagnosis were more often treated with chemotherapy. Second-line median PFS was 6.4 months (95% CI [5.0-12.9]) for chemotherapy and 8.4 months (95% CI [5.4-11.7]) for ET ± targeted therapy, with no significant difference (HR 1.08, 95% CI [0.73-1.59], p = 0.70).

CONCLUSION: This French real-world study demonstrates limited progression-free survival benefits across all second-line strategies after CDK4/6 inhibitor progression, highlighting an urgent clinical need for more effective post-progression therapies.