Augmentium Pharma Consulting (Canada)

Patients receiving moderately emetogenic chemotherapy (MEC) are commonly prescribed a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist (RA) and dexamethasone (DEX) as standard-of-care (SOC) antiemetic prophylaxis. However, in patients with an elevated risk of chemotherapy-induced nausea and vomiting (CINV) due to individual risk factors, prophylaxis with an neurokinin-1 (NK1) RA-containing regimen may optimise their antiemetic prevention. To address this unmet need for a more personalised antiemetic strategy, the MyRisk trial incorporated a predictive risk factor algorithm to select patients at increased risk of CINV who may benefit from enhanced antiemetic prophylaxis. MyRisk was a phase IV, randomised, open-label, multicentre, multinational trial. Adult patients scheduled to receive three cycles of MEC with a high-risk CINV score were randomly assigned to NEPA (a fixed combination of an NK1 RA, netupitant, and 5-HT3 RA, palonosetron) + DEX or SOC. The CINV risk score was calculated based on an algorithm that considered seven risk factors. The primary endpoint was complete response (CR: no emesis/no rescue medication) during the overall phase (0-120 h) across three consecutive cycles. Of 401 randomly allocated patients, 388 were included in the efficacy analysis. The most common cancers were colorectal and lung; oxaliplatin and carboplatin were the most common MECs. Patients randomly assigned to NEPA were significantly more likely to experience a CR compared with SOC (odds ratio 1.67, 95% confidence interval 1.12-2.49, P = 0.012). The NEPA group had a significantly higher probability of CR, no nausea, no emesis, and complete protection (81.0%, 63.7%, 95.4%, and 71.8%, respectively) compared with the SOC arm (71.8%, 54.9%, 86.7%, and 62.4%, respectively) across three cycles of chemotherapy. When individual risk factors are considered before MEC, a three-drug regimen including NEPA provides superior CINV prevention across multiple cycles compared with the standard two-drug approach. These findings underscore the value of personalised risk-adapted antiemetic strategies and have practice-changing potential for optimising antiemetic control.

BackgroundLanreotide and octreotide acetate suspension for injectable (LAR) are bothrecommended for clinical use in patients with locally advanced or metastaticgastroenteropancreatic neuroendocrine tumors. However, each agent possessesunique attributes in terms of their drug-delivery characteristics. The studyobjective was to compare overall drug-delivery efficiency between lanreotideand octreotide LAR in gastroenteropancreatic neuroendocrine tumorpatients.MethodsThis study employed an observational time and motion design among patientstreated with lanreotide or octreotide LAR across five US cancer centers.Baseline patient data collection included age, disease grade and duration,prior therapies and performance status. Drug-delivery time (drug preparationand administration), total patient time and resource use data were collectedfor gastroenteropancreatic neuroendocrine tumors receiving lanreotide(n = 22) or octreotide LAR (n = 22). Following each administration,qualitative data on the drug-delivery experience was collected from patientsand nurses.ResultsLanreotide was associated with a significant reduction in mean delivery time(2.5 min; 95% CI:2.0 to 3.1) compared to octreotide LAR (6.2 min; 95%CI: 4.4to 7.9; p = 0.004). The mean total patient time forlanreotide and octreotide LAR was comparable between groups (32.1 vs. 36.6minutes; p = 0.97). Nurses reported increased concerns withoctreotide LAR related to needle clogging (p = 0.034) anddevice failures (p = 0.057). Overall, lanreotide had amedian satisfaction score of 5.0 compared to a score of 4.0 with octreotideLAR (p = 0.03).ConclusionsLanreotide was associated with significant reductions in drug-delivery timecompared to octreotide LAR, which contributed to an improvement in overallhealthcare efficiency.Trial registrationclinicaltrials.gov Identifier: NCT03017690.

ABSTRACTIntroduction: After years of setback, cancer immunotherapy has begun to yield clinical dividends, which are changing the treatment landscape and offering cancer patients the potential for long-term survival, reduced treatment-related toxicity and improved quality-of-life. Using the immune system to treat cancer is known as ‘Immuno-oncology’ (IO) and agents are sub-classified by their ability to enhance anti-tumor response or to direct the immune system to attack cancer cells via tumor-associated antigens.Areas covered: Clinical trials have demonstrated the effectiveness of several IO agents in many disease sites such as early and advanced stage melanoma, advanced non-small cell lung cancer, bladder, head and neck, gastric, kidney as well as Hodgkin’s lymphoma. Notwithstanding the therapeutic excitement generated for patients and clinicians alike, an important consideration is treatment cost, which can reach more than $US100,000 per patient annually. The cost of the drugs, coupled with high disease prevalence and the ever-expanding number of indications, means the current cost trajectory is untenable for most healthcare systems to sustain.Expert commentary: In this paper, the approved IO drugs and those in clinical development are reviewed. The issue of cost effectiveness vs. affordability is then addressed and suggestions that facilitate patient access and long-term sustainability are presented.

In a randomized trial (ie, Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer [CLOT]) that evaluated secondary prophylaxis of recurrent venous thromboembolism (VTE) in patients with cancer, dalteparin reduced the relative risk by 52% compared to oral vitamin K antagonists (VKAs; hazard ratio = 0.48, P = .002). A recent subgroup analysis in patients with moderate to severe renal impairment also revealed lower absolute VTE rates with dalteparin (3% vs 17%; P = .011). To measure the economic value of dalteparin in these populations, a pharmacoeconomic analysis was conducted from the Dutch health-care system perspective. Resource utilization data contained within the CLOT trial database were extracted and converted into direct cost estimates. Univariate analysis was then conducted to compare the total cost of therapy between patients randomized to dalteparin or VKA therapy. Health state utilities were then measured in 24 members of the general public using the time trade-off technique. When all of the cost components were combined for the entire population (n = 676), the dalteparin group had significantly higher overall costs than the VKA control group (dalteparin = €2375 vs VKA = €1724; P < .001). However, dalteparin was associated with a gain of 0.14 (95% confidence interval [CI]: 0.10-0.18) quality-adjusted life years (QALYs) over VKA. When the incremental cost was combined with the utility gain, dalteparin had a cost of €4,697 (95% CI: €3824-€4951) per QALY gained. Secondary prophylaxis with dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer.

e18238Background: Patients with cancer who develop thrombosis are at increased risk for recurrent VTE. To reduce this risk, prolonged prophylaxis with VKA may be offered. However in a randomized tr...

Pulmonary arterial hypertension (PAH) is a rare but life-threatening condition that is characterized by progressive elevation of pulmonary artery pressure and pulmonary vascular resistance, leading to right-sided heart failure and frequently death. Orally administered agents used for the treatment of symptomatic, moderate-to-severe PAH include sildenafil and the endothelin (ET) receptor antagonists (ERAs), bosentan and sitaxentan (sitaxsentan). Ambrisentan is a new oral ET(A) receptor-selective ERA, with higher ET receptor affinity than bosentan. Placebo-controlled, randomized clinical trials (RCTs) have demonstrated that ambrisentan (5 or 10 mg/day) is safe and effective. To provide health economic data on the multiple oral PAH therapies currently available, a population-based cost-minimization analysis (CMA) was conducted for Canada. The primary requirement for a CMA is that all clinical outcomes be equivalent between comparator treatments. To provide such supporting data, a literature search was conducted for RCTs of oral agents used to treat symptomatic PAH. This was followed by application of direct and indirect statistical methods to support the hypothesis of clinical equivalence between the oral agents. Estimates for PAH prevalence, incidence and death rates were then used to build a population-based CMA model. The base-case analysis considered costs for drug therapy, outpatient pharmacy costs, medical consultations and visits, laboratory and diagnostic procedures and other healthcare-related resources. In addition, costs for secondary pharmacotherapy in cases where the primary agent had to be discontinued because of adverse effects were also included. The time horizon for evaluating pharmacotherapy was 3 years, all costs were in 2008 Canadian dollars ($Can) and the costs were discounted at a rate of 3% annually. The study perspective was the Canadian healthcare system. There were no double-blind RCTs comparing ambrisentan with any of the other oral agents. Therefore, an indirect comparison of placebo-controlled trials of PAH drugs had to be used to support the clinical equivalence. This included a calculation of standardized mean differences (SMD) between agents (vs placebo) and a meta-regression analysis on the primary and secondary trial endpoints. Keeping in mind the caveats associated with indirect trial comparisons, the data suggested similar clinical efficacy over 12-16 weeks between agents, as indicated by the identical magnitude of the SMD between the active agent and placebo and the non-significant differences between drugs as determined by the meta-regression analysis. The population-based model projected that the number of PAH patients clinically suitable for these drugs in Canada would be 931 in the first full-budget year (i.e. 2009) with an increase to 1114 by the third full year. The CMA revealed the following rank order of the least to most costly agent; sildenafil, ambrisentan, sitaxentan and bosentan. Sildenafil was the least costly, primarily because of the lower daily drug-acquisition cost. Of the three ERAs, ambrisentan would be associated with annual cost savings of $Can3.4 and $Can5.6 million when used as an alternative to sitaxentan or bosentan, respectively. Ambrisentan is less costly than other available ERAs, including bosentan and sitaxentan, but is more costly than sildenafil. In PAH patients in whom an ERA is the preferred agent, ambrisentan may be the drug of choice because of its economic advantages and improved safety profile.