Neoadjuvant chemotherapy with or without nintedanib for advanced epithelial ovarian cancer: Lessons from the GINECO double-blind randomized phase II CHIVA trial.

AIM: The oral anti-angiogenic therapy nintedanib prolongs progression-free survival (PFS) when combined with chemotherapy after primary surgery for advanced epithelial ovarian cancer. The randomized phase II CHIVA trial evaluated the impact of combining nintedanib with neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer. METHODS: Patients with newly diagnosed unresectable FIGO stage IIIC-IV epithelial ovarian cancer received 3-4 cycles of carboplatin plus paclitaxel every 3 weeks as NACT before interval debulking surgery (IDS), followed by 2-3 post-operative cycles. Patients were randomized 2:1 to receive either nintedanib 200 mg twice daily or placebo on days 2-21 every 3 weeks during NACT (omitting peri-operative cycles), and then as maintenance therapy for up to 2 years. The primary endpoint was PFS. RESULTS: Between January 2013 and May 2015, 188 patients were randomized (124 to nintedanib, 64 to placebo). PFS was significantly inferior with nintedanib (median 14.4 versus 16.8 months with placebo; hazard ratio 1.50, p = 0.02). Overall survival (OS) was also inferior (median 37.7 versus 44.1 months, respectively; hazard ratio 1.54, p = 0.054). Nintedanib was associated with increased toxicity (grade 3/4 adverse events: 92% versus 69%, predominantly hematologic and gastrointestinal), lower response rate by RECIST (35% versus 56% before IDS), and lower IDS feasibility (58% versus 77%) versus placebo. CONCLUSIONS: Adding nintedanib to chemotherapy and in maintenance as part of NACT for advanced epithelial ovarian cancer cannot be recommended as it increases toxicity and compromises chemotherapy efficacy (IDS, PFS, OS). CLINICALTRIALS: govregistration: NCT01583322.

Zarzio®, biosimilar of filgrastim, in prophylaxis of chemotherapy-induced neutropenia in routine practice: a French prospective multicentric study.

PURPOSE: Chemotherapy-induced neutropenia is a serious and potentially life-threatening consequence of cancer treatment. Prophylactic treatment with granulocyte-colony stimulating factor (G-CSF) decreases the incidence of febrile neutropenia, the rate of hospitalization, and the use of antibiotics in patients at risk. The aim of this study was to assess efficacy, safety, and use of Zarzio(®)-biosimilar of Neupogen(®) (G-CSF; filgrastim)-in prophylaxis of chemotherapy-induced neutropenia in current practice in cancer patients. METHODS: We conducted an observational, prospective, longitudinal, and multicentric study in France. The incidence of neutropenia was evaluated at each cycle of chemotherapy. RESULTS: One hundred eighty-four patients (women, 64.7 %; mean age, 61.7 years) with solid tumor (89.7 %; breast cancer, 50.5 %) or non-Hodgkin lymphoma (10.3 %) were included. The risk of febrile neutropenia based on chemotherapy regimen was >20 % for 32.1 % of patients. No case of febrile neutropenia was reported. Neutropenia was the cause of hospitalization and/or antibiotic therapy in 10 patients. The most frequent adverse events related to Zarzio(®) were pain, in particular bone pain. No serious adverse event related to Zarzio(®) was reported. CONCLUSION: The results obtained in real-life conditions confirm that Zarzio(®) is efficient and well tolerated in cancer patients.