الفهرس 
Epidemiology of Breast CancerOnly 14 pages are availabe for public view
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Abstract
Background: Combination therapies are becoming the new standard of care in treatment hormonal receptor (HR) positive human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer (ABC) patients. Most of the new drugs impose great financial burden especially in low-middle income countries. The need for studies to explore less expensive combinations is becoming crucial.
Patients and methods: In this prospective randomized phase II study: we randomly assigned 95 patients with HR positive, Her 2 negative ABC, who didn’t receive previous systemic endocrinal treatment for advanced disease in both arms, to receive aromatase inhibitor (AI) or capecitabine (625 mg/m2 bid PO for 14 days to be repeated every 21 days) plus AI administered daily. The primary endpoint was progression free survival (PFS) and secondary end point was toxicity.
Results: The median PFS was 18.7 months for the capecitabine plus AI (CapAI) arm versus 9.8 months for the AI only arm with a p value of 0.009 with a hazard ratio (HR) of 0.46 (95% CI 0.25-0.82).The median duration of follow up was 16.8 months (95% CI for the median; 14.1 to 17.9 months). The median number cycles of capecitabine received was was 12.3 cycles (range 0-38.4). Subgroup analysis revealed significant difference in favor of the CapAI arm for the premenopausal patients (p=0.04), visceral only and non-visceral only metastasis (p= 0.05, 0.04), non-oligometastatic patients (p=0.002) and patients who received treatment as first line (p= 0.02). Non-significant difference in PFS was found in the following subgroups; postmenopausal (p=0.05), bone only metastasis (p=0.22), oligometastatic (p=0.66), primary and secondary hormonal resistant patients (p=0.07, 0.07) and patients who received treatment beyond first line (p=0.32). There was no significant difference in the rates of toxicity in both arms regarding hematological toxicity (anemia, thrombocytopenia and neutropenia), fatigue, nausea, vomiting, diarrhea, mucositis. But there was significant difference in the hand foot syndrome (grade 1/2) with the 15.4% in the CapAI arm versus 0 % in the AI only arm, peripheral neuropathy (grade 1/2) with 23.1% vs 4.3% and hepatic toxicity (grade 1) 10.3% vs 0 %. Grade 3 toxicity was reported in only 3 patients in our study all in the CapAI arm (fatigue, thrombocytopenia and neutropenia). No permanent discontinuation occurred but 25% dose reduction was done in four patients due to decrease in creatinine clearance.
Conclusion: Among patients with HR positive Her2 negative ABC, combination of capecitabine with AIs showed significant improvement in median PFS than AI alone. With good tolerability and acceptable toxicity profile. Capecitabine AI combination might turn out to be the new standard of care for treatment of MBC patients. We recommend further studies with larger number of patients to be done evaluating combination therapy as first and second line treatment for ABC. ClinicalTrials.gov number NCT04012918