Maximizing the benefits of using biosimilars in Egypt.

BACKGROUND: Biosimilars constitute a pathway for sustainable financing of healthcare systems in the era of expensive biologics. However, such a pathway is not free of challenges. Since the biosimilars market is expanding in Egypt, there is an urgent need for a policy framework to optimize their use and diffusion in the market. We aim to characterize a national framework based on the experiences of other countries and consultation with local experts. METHODS: A narrative literature review was conducted to identify biosimilars' policy elements worldwide. A workshop was organized with experts to discuss the narrative review findings and create consensus on recommendations. RESULTS: The narrative literature review highlighted the need for biosimilar policy actions in four areas: market authorization, pricing, reimbursement, and uptake. Eighteen experts representing the Egyptian healthcare authorities attended the workshop. The most significant conclusions from the workshop included setting the price of the biosimilar at 30-40% less than its originator's price and establishing financing protocols, in which the more expensive biologics with significant price premiums should be excluded from the formulary. CONCLUSIONS: A summarized national framework policy recommendation for biosimilars was created by local experts from the main public healthcare entities in Egypt. These recommendations coincide with the international policies adopted across different countries that aim to improve patient access while sustaining health expenditure.

The effect of itraconazole on the clinical outcomes of patients with advanced non-small cell lung cancer receiving platinum-based chemotherapy: a randomized controlled study.

Itraconazole is an oral antifungal that has a been reported to have anticancer effect in non-small cell lung cancer (NSCLC) through inhibition of angiogenesis. The aim is to evaluate the effect of using itraconazole on the clinical outcome of metastatic NSCLC. This was a prospective randomized controlled open-label study conducted on 60 chemotherapy-naive metastatic NSCLC. Patients were simply randomized to either Control group who received platinum-based chemotherapy for a maximum of six cycles or Itraconazole group who received the same chemotherapy regimen in addition to itraconazole 200 mg daily for 21 days starting from day 1 in each cycle. Primary outcome was 1-year progression-free survival (PFS) while secondary outcomes included overall response rate (ORR), 1-year overall survival (OS) and tolerability. The two groups were comparable at baseline with no significant difference between groups regarding demographics and clinical characteristics. The ORR in Control group was 66.7% versus 90% in Itraconazole group (p value 0.028). There was a significant difference between groups regarding PFS where the mean 1-year PFS was 5.415 months in Control group versus 6.556 months in Itraconazole group (p value = 0.002). However, there was no significant difference between groups with respect to 1-year OS. All adverse effects reported were tolerable except for one patient who developed grade 2 cardiotoxicity in Itraconazole group requiring itraconazole discontinuation. Itraconazole use was beneficial in NSCLC in terms of 1-year PFS and ORR which was not reflected by improvement in 1-year OS.Clinical trial.gov registration number: NCT03664115, date of registration: September 10, 2018.

Doxorubicin-loaded nanoparticles for patients with advanced hepatocellular carcinoma after sorafenib treatment failure (RELIVE): a phase 3 randomised controlled trial.

BACKGROUND: Cytotoxic chemotherapy is generally ineffective in patients with hepatocellular carcinoma. We assessed the intravenous perfusion of doxorubicin-loaded nanoparticles in patients with hepatocellular carcinoma in whom previous sorafenib therapy had failed. METHODS: We did a multicentre, open-label, randomised, controlled phase 3 trial at 70 sites in 11 countries. Patients with hepatocellular carcinoma with one or more previous systemic therapies, including sorafenib, were randomly assigned to receive 30 mg/m2 doxorubicin-loaded nanoparticles (30 mg/m2 group), 20 mg/m2 doxorubicin-loaded nanoparticles (20 mg/m2 group), or standard care using a computer-generated randomisation list prepared by the funder and stratified by geographic region. Patients in the experimental groups received perfusion of the drug every 4 weeks and those in the control group received any systemic anticancer therapy (except sorafenib) as per investigator decision. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the population of patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT01655693. FINDINGS: Between June 15, 2012, and Jan 27, 2017, 541 patients were screened, of whom 144 were excluded and 397 were randomly assigned to one of the groups (133 to the 30 mg/m2 group; 130 to the 20 mg/m2 group; and 134 to the control group). Median follow-up was 22·7 months (IQR 11·2-34·9). After pooling the doxorubicin groups for the efficacy analysis, median overall survival was 9·1 months (95% CI 8·1-10·4) in the pooled doxorubicin-loaded nanoparticles group and 9·0 months (7·1-11·8) in the control group (HR 1·00 [95% CI 0·78-1·28], two-sided p=0·99). 227 (94%) of 242 patients who received doxorubicin-loaded nanoparticles and 100 (75%) of 134 patients in the control group had at least one treatment-emergent adverse event. The most common drug-related grade 3 or 4 treatment-emergent adverse events were neutropenia (25 [10%] of 242 treated with doxorubicin-loaded nanoparticles and eight [6%] of 134 in the control group), asthenia (six [2%] and four [3%]), and thrombocytopenia (three [1%] and ten [7%]). Six (2%) patients treated with doxorubicin-loaded nanoparticles and one (1%) of those in the control group were deemed by investigators to have had a drug-related death. Serious adverse events occurred in 74 (31%) patients who received doxorubicin-loaded nanoparticles and 48 (36%) in the control group. INTERPRETATION: Doxorubicin-loaded nanoparticles did not improve overall survival for patients with hepatocellular carcinoma in whom previous sorafenib treatment had failed. FUNDING: Onxeo.

A prospective randomized controlled study of cisplatin versus carboplatin-based regimen in advanced squamous nonsmall cell lung cancer.

BACKGROUND: The use of cisplatin (Cis) versus carboplatin (Carb) in the treatment of advanced nonsmall cell lung cancer (NSCLC) is controversial. The aim of the study was to compare the safety and efficacy of Cis versus Carb in squamous NSCLC. PATIENTS AND METHODS: A prospective, randomized, controlled, open-label study was conducted on advanced squamous NSCLC patients who were randomly assigned to receive Cis (40 mg/m 2 [day 1 and day 8]) or Carb (area under the curve = 5 [day 1]) combined with gemcitabine [Gem] (1000 mg/m 2 [day 1 and day 8]) of a 3-week schedule for six cycles. Study objectives were a radiological response after three cycles and six cycles, 1-year progression-free survival (PFS), 1-year overall survival (OS), and quality of life (QOL) assessment using functional assessment of cancer therapy-lung at baseline, after three cycles, and after six cycles. STATISTICAL ANALYSIS: Statistical analysis was done using Statistical Package for Social Science version 15. A P < 0.05 was considered statistically significant. RESULTS: Seventy-one patients were enrolled (Gem/Cis group [n = 36], Gem/Carb group [n = 35]). Response rates were comparable in both arms. Nonsignificant differences were found regarding 1-year PFS (P = 0.308) and 1-year OS (P = 0.929) between the two groups. Neutropenia was significantly higher in Gem/Carb group, while vomiting and ototoxicity were significantly higher in Gem/Cis group. The effect on QOL was similar in both groups. CONCLUSION: Cis and Carb have similar efficacy, tolerability, and effect on QOL and both can be used as a first-line treatment of squamous NSCLC.