Metronomic oral chemotherapy with cyclophosphamide plus capecitabine combined with trastuzumab (HEX) as first line therapy of HER-2 positive advanced breast cancer: A phase II trial of the Gruppo Oncologico Italia Meridionale (GOIM). (October 2020)

• Record Type: Journal Article
• Authors: Orlando, Laura; Lorusso, Vito; Giotta, Francesco; Di Maio, Massimo; Schiavone, Paola; Fedele, Palma; Quaranta, Annamaria; Caliolo, Chiara; Ciccarese, Mariangela; Cinefra, Margherita; Romito, Sante; Pisconti, Salvatore; Prete, Salvatore del; Aieta, Michele; Rizzi, Daniele; Maiello, Evaristo; Colucci, Giuseppe; Cinieri, Saverio
• Is Part Of: Breast. Volume 53(2020)
• Page Start: 18
• Page End: 22
• Publication Date: 2020-10
• Subjects: HER-2 positive -- Metronomic chemotherapy -- Advanced breast cancer; Breast -- Diseases -- Periodicals; Breast -- Tumors -- Periodicals; Breast -- Periodicals; Electronic journals; Periodicals; 616
• DOI: 10.1016/j.breast.2020.06.002
• Languages: English
• ISSNs: 0960-9776

Abstract

Abstract: Background. The combination of chemotherapy plus anti HER-2 agents is the mainstay of HER-2 positive advanced breast cancer (ABC) therapy. We conducted a phase II trial testing activity and safety of trastuzumab and metronomic capecitabine/cyclophosphamide (HEX) as first-line therapy in HER-2 positive ABC. Methods. Patients at first relapse or with synchronous metastasis were treated with trastuzumab (4 mg/kg, biweekly) plus oral capecitabine (1500 mg/daily) and cyclophosphamide (50 mg/daily). Primary endpoint was objective response rate (ORR), secondary endpoints progression-free survival (PFS), clinical benefit rate (CBR; PR + CR + SD for ≥ 24 weeks) and tolerability. Optimal two-stage design was applied. Results. Sixty patients with measurable ABC, tumors scored as +3 for HER-2 or FISH +, untreated for advanced disease were enrolled. Median age was 62.5 years, visceral metastases were present in most patients (57.9%). Median number of cycles was 16 (range 1–98). ORR was 56.7% (95% CI, 44.1–68.4%), with 5 CR (8.3%) and 29 PR (48.3%). Fifteen patients had SD (25%). The CBR was 78.2%. Nine progressions were observed (15%). Median PFS was 11 months. One year PFS was 47.7%. Median OS was 45.9 months. Worst toxicities were grade 3 hand-foot syndrome in 2 pts (3.3%), grade 3 anaemia in 2 pts (3.3%), grade 2 nausea in 2 pts (3.3%) and grade 3–4 diarrhea in 2 pts (3.3%). Cardiac toxicity grade 1 was reported in 1 pt. Conclusions. Combination of trastuzumab and metronomic oral chemotherapy has clinical activity. The tolerability was excellent and allowed the prolonged delivery of treatment. Highlights: Combination of chemotherapy plus anti HER-2 agents is the standard treatment of HER-2 positive breast cancer. Combination of trastuzumab and metronomic chemotherapy is an alternative therapeutic approach. Metronomic therapy allows long-term administration of drugs. Mild toxicity in advanced breast cancer is desirable.