62P - Combination of chemotherapy with endocrinal therapy as upfront treatment of metastatic breast cancer in hormone receptor- positive, HER2 -negative disease: A phase II randomised clinical trial

Background

First line endocrine therapy is the gold standard for advanced ER- positive, HER2 -negative breast cancer. Adding CDK4/6 inhibitors has improved PFS with several challenges to adopt for all patients. Metronomic Capecitabine has proven to be safe to combine with endocrine therapy with promising efficacy.

Methods

We conducted a phase II randomised, open label, single centre clinical trial on patients with metastatic ER- positive, HER -2 negative breast cancer. Eligible patients were randomised (1:1) to arm A: metronomic dose of capecitabine (500mg/m² BID) with letrozole (2.5mg OD) or arm B: letrozole alone. The primary endpoint was progression free survival. The study was terminated early due to poor accrual and 60 eligible patients out of the planned 204 were randomized.

Results

Between February 2019 and April 2022, 60 patients were randomized. This is the first report of the study, after a median follow-up of 18.6 months. The median age at diagnosis was 47 years with only 41.7% of patients post-menopausal. Half of our patients had bone-only disease, 45% had visceral metastasis (liver and lung) and 63% presented with endocrine sensitive disease. The estimated median PFS for the whole population was 16.2 months. Median PFS for capecitabine arm was 17.7 months versus 14.6 months for letrozole alone (p = 0.078). Overall response rate was 70% for capecitabine/letrozole arm and 56.6% for letrozole only. Clinical benefit rate was 90% in the capecitabine/letrozole arm versus 73.3% in the letrozole arm. Overall survival data is still immature after this short follow up duration. Adverse event assessment showed acceptable all grade and high grade toxicity profile consistent with the established adverse events of both capecitabine and letrozole. Anaemia (28.3%) and hand & foot syndrome (43.8%) were significantly more common in the capecitabine/letrozole arm.

Conclusions

Capecitabine combined with letrozole have showed a trend towards improvement in progression free survival with potential more benefit to certain sub-groups and the combination showed acceptable safety profile consistent with the established known safety profile of both letrozole and capecitabine.

Clinical trial identification

MD-127-2019, NCT04571437.

Editorial acknowledgement

Legal entity responsible for the study

Ethics committee at the Faculty of Medicine, Cairo University.

Funding

Has not received any funding.

Disclosure

L. Kassem, H.A. Azim: Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, Novartis, Janssen, Pfizer, Eva, Sandoz, Hikma, MSD. All other authors have declared no conflicts of interest.