G-CSF filgrastim biosimilar-Sandoz reduces the incidence of febrile neutropenia in patients receiving chemotherapy regimens with rest periods not exceeding 14 days: A French, multicenter, prospective, non-interventional study

Purpose: The objective of this study was to describe filgrastim biosimilar-Sandoz modalities of use in patients receiving cytotoxic chemotherapy regimens with a rest period of ≤14 days and to investigate the incidence of febrile neutropenia (FN) in routine clinical practice. Methods: This was a French, multicenter, prospective and descriptive, non‐interventional study including patients with breast, lung, gastrointestinal cancer or a lymphoma initiating filgrastim biosimilar-Sandoz treatment and in the context of cytotoxic chemotherapy with a rest period not exceeding 14 days. Data were collected during two routine clinical visits on the modalities of use of filgrastim biosimilar-Sandoz, on the incidence of neutropenia events and on adverse events. Results: Between November 2015 and June 2018, 1080 patients were enrolled in the study in 129 centers. Overall, 941 patients were evaluable for efficacy and 937 for safety. Of the 941 patients, 84.8% had a solid tumor and 15.2% had a lymphoid hemopathy. Filgrastim biosimilar-Sandoz was prescribed as primary prophylaxis in 74.0% of the patients and as secondary prophylaxis in 22.4% of the patients. FN was reported in 1.5% of patients with a solid tumor and 12.6% of patients with a lymphoma. A chemotherapy relative dose intensity of over 85% with regard to the reference dose was achieved by more than 80% of the patients in all tumor localizations. Conclusions: The study showed that filgrastim biosimilar-Sandoz is safe to use and effective in preventing FN and in allowing to maintain the dose intensity of chemotherapy

Intra-Arterial Delivery of Idarubicin in Two Patients with Glioblastoma

There is no effective treatment for recurrent glioblastoma (GB) when temozolomide-based radiochemotherapy fails. In theory, intra-arterial (IA) delivery of cytotoxic agents could achieve higher drug concentrations in tumors compared to intravenous injection. Moreover, choosing a highly lipid-soluble drug could make the most of the first-pass effect. Here, we evaluated idarubicin (IDA), a lipophilic anthracycline, in an in vitro assay using four human GB cell lines and compared it with 11 other drugs previously used for the IA treatment of brain tumors. Despite impressive in vitro cytotoxicity, IA IDA did not produce a beneficial effect in 2 patients with recurrent GB

Resection of small bowel adenocarcinoma metastases: Results of the ARCAD-NADEGE cohort study

International audienceINTRODUCTION:Data are lacking with regard to curative resection of metastasis from small bowel adenocarcinoma (SBA). This study evaluated outcomes and prognostic factors in patients with curatively resected metastatic SBA.METHODS:A series of 34 patients undergoing resection of metastatic SBA from January 2009 to November 2014 at French centers were included into this cohort study. The primary endpoint was overall survival (OS). Secondary endpoints were recurrence-free survival (RFS) and prognostic factors. Univariate analyses were performed to determine prognostic risk factors.RESULTS:The sites of SBA metastases were peritoneal (29.4%), liver (26.5%), lymph nodes (11.8%), lung (2.9%), multiple (14.7%), and other (14.7%). Thirty (88.2%) patients received adjuvant or perioperative chemotherapy, mainly was oxaliplatin-based (76.5%). The median OS was 28.6 months and RFS was 18.7 months. Fourteen (41.2%) patients survived for more than 36 months. In univariate analysis, poor differentiation (P = 0.006), invaded margins (P = 0.003), and lymphatic invasion in the primary tumor (P = 0.039) were associated with decreased OS.CONCLUSION:Overall survival of patients after resection of metastatic SBA remains poor, but long-term survivors are observed. Resection of metastatic SBA should be consider if patients are expected to be operated on with curative intent and have moderately or well-differentiated tumors

Clinical effectiveness of olaparib monotherapy in germline BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: phase IIIb LUCY interim analysis

© 2021 Elsevier LtdBackground: In the phase III OlympiAD trial, olaparib significantly increased progression-free survival (PFS) compared with chemotherapy of physician's choice in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (mBC). The phase IIIb LUCY trial assessed the clinical effectiveness of olaparib in similar patients, in a setting reflecting clinical practice. Methods: This open-label, single-arm trial of olaparib (300 mg, twice daily) enrolled patients with BRCAm, HER2-negative mBC who had received taxane and/or anthracycline in the (neo)adjuvant/metastatic setting and not more than two lines of prior chemotherapy for mBC. Patients with hormone receptor–positive mBC had progressed on at least one line of endocrine therapy in an adjuvant/metastatic setting and were unsuitable for further endocrine treatment. This interim analysis was planned after 160 PFS events. Results: Of 563 patients screened, 252 patients with gBRCAm were enrolled and received at least one dose of olaparib. The median investigator-assessed PFS was 8.11 months (95% confidence interval [CI], 6.93–8.67; 166/252 events [65.9% maturity]). The investigator-assessed clinical response rate was 48.6%, and median time to first subsequent treatment or death was 9.66 months (95% CI, 8.67–11.14). The most common treatment-emergent adverse events (TEAEs; >20% patients) were nausea, anaemia, asthenia, vomiting and fatigue. Eleven patients (4.4%) discontinued treatment because of a TEAE. Grade 3 or higher TEAEs occurred in 64 patients (25.4%), including anaemia (33 patients; 13.1%). Conclusion: Olaparib was clinically effective in patients with gBRCAm, HER2-negative mBC with safety outcomes consistent with previous findings. ClinicalTrials.gov identifier: NCT03286842.

Clinical effectiveness and safety of olaparib in BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: final analysis of LUCY

PurposeThe interim analysis of the phase IIIb LUCY trial demonstrated the clinical effectiveness of olaparib in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC), with median progression-free survival (PFS) of 8.11 months, which was similar to that in the olaparib arm of the phase III OlympiAD trial (7.03 months). This prespecified analysis provides final overall survival (OS) and safety data.MethodsThe open-label, single-arm LUCY trial of olaparib (300 mg, twice daily) enrolled adults with gBRCAm or somatic BRCA-mutated (sBRCAm), HER2-negative mBC. Patients had previously received a taxane or anthracycline for neoadjuvant/adjuvant or metastatic disease and up to two lines of chemotherapy for mBC.ResultsOf 563 patients screened, 256 (gBRCAm, n = 253; sBRCAm, n = 3) were enrolled. In the gBRCAm cohort, median investigator-assessed PFS (primary endpoint) was 8.18 months and median OS was 24.94 months. Olaparib was clinically effective in all prespecified subgroups: hormone receptor status, previous chemotherapy for mBC, previous platinum-based chemotherapy (including by line of therapy), and previous cyclin-dependent kinase 4/6 inhibitor use. The most frequent treatment-emergent adverse events (TEAEs) were nausea (55.3%) and anemia (39.2%). Few patients (6.3%) discontinued olaparib owing to a TEAE. No deaths associated with AEs occurred during the study treatment or 30-day follow-up.ConclusionThe LUCY patient population reflects a real-world population in line with the licensed indication of olaparib in mBC. These findings support the clinical effectiveness and safety of olaparib in patients with gBRCAm, HER2-negative mBC.Clinical trial registrationClinical trials registration number: NCT0328684