Gilberto de Lima Lopes

Major breakthroughs have been realized in controlling cancer in the past five decades. However, for patients in low- and middle-income countries (LMICs), many of these advances are nothing but an aspiration and hope for the future. Indeed, the greatest challenge we face in oncology today is how to reconcile small, incremental and significant improvements in the management of cancer with the exponentially increasing costs of new treatments. Emerging economies are attempting to address this important issue of access to cancer medications. In this Review, we examine how LMICs are using generic and biosimilar drugs, expanding participation in clinical trials, implementing universal health-care schemes to pool resources, and using compulsory licensing schemes as well as increasing multiple-stakeholder public-private partnerships to increase access to cancer medications for their citizens. Any truly effective programme will require multiple stakeholder involvement-including governments, industry and civil society-to address the issue of access to medication. Only with the creation of a global entity to fight cancer that is supported by a global fund-for example, in the mould of the GAVI alliance and the International Finance Facility for Immunization-will we truly be able to improve cancer care in LMICs and drive down the high mortality rates in these regions.

Fulvestrant is a highly active systemic therapy in patients with metastatic hormone receptor positive breast cancer. Preclinical work suggested potential synergy of fulvestrant in combination with aromatase inhibitor therapy and delayed development of endocrine resistance. The purpose of this meta-analysis is to evaluate the effectiveness of fulvestrant plus anastrozole, compared to anastrozole alone, as first line treatment of postmenopausal stage IV hormone receptor positive, HER2-negative breast cancer. The literature search was performed using PubMed, Google Scholar, Embase, ASCO, and ESMO to search for abstracts published during the last 10 years using relevant keywords. Two prospective randomized clinical trials were found to fulfill the search criteria for combination of anastrozole plus fulvestrant versus anastrozole alone. Meta-estimates were calculated by combining study estimates using the DerSimonian and Laird random effects model. The linear mixed-effects model was used to generate 95 % prediction intervals (PIs) for study-specific hazard and odds ratios. Pooled hazard ratio for progression-free survival is 0.88 (95 % CI 0.72–1.09, 95 % PI 0.65–1.21), overall survival 0.88 (95 % CI 0.72–1.08, 95 % PI 0.68–1.14) and pooled odds ratio for response rate is 1.13 (95 % CI 0.79–1.63, 95 % PI 0.78–1.65). A non-significant trend was observed with anastrozole plus fulvestrant being only marginally better than anastrozole alone in the endpoints of: progression-free survival, overall survival, and response rates. Based on these data, there is not solid evidence that the addition of fulvestrant at a dose of 250 mg monthly is better than anastrozole alone as first line therapy in women with postmenopausal hormone receptor positive breast cancer.

576 Background: C225, a monoclonal antibody against the epidermal growth factor receptor, has been shown to inconsistently improve response rates (RR), progression-free survival (PFS) and overall survival (OS) in the first-line treatment of advanced CRC Pts with K-ras WT tumors. Methods: We performed a meta-analysis of four trials where K-ras WT Pts received a Fp (capecitabine (C) or bolus (b) or infusional (CI) 5-fluorouracil (5-FU)) and oxaliplatin (oxali) or irinotecan (CPT) ± C225 (CRYSTAL, OPUS, COIN and NORDIC VII trials) and one trial, where K-ras WT and mutant Pts received C225 with capecitabine (C) and oxali or CPT (AIO study). We sought to determine if the choice of Fp affects the response to C225. A mixed effects model similar to that of DerSimonian and Laird was fit by restricted maximum likelihood and used to obtain an overall estimate of the effect of C225 in the presence of CI 5-FU, an indirect estimate of the decrease in the effect of C225 in the presence of C/b5-FU relative to CI 5-FU, and an estimate of the study-to-study variability. Results: Only Pts treated with CI 5-FU based chemo derived benefit from C225. Relative to CI 5-FU, Pts treated with C or b5-FU based doublet chemo had a decrease in RR, PFS and OS. The choice of oxali or CPT did not affect responses to C225. Conclusions: The lack of benefit for C225 with C or b5-FU chemo is unexpected. A possible explanation is increased toxicity with C225, which led to dose reduction of C only in the C225-arm of the COIN study; however, increased toxicity was not seen in the NORDIC VII study. Pending further study, only CI 5-FU regimens should be used with C225. [Table: see text]

311 Background: Advanced pancreatic cancer (PC) is a virulent disease, where gemcitabine is considered the standard-of-care. A recent phase III evaluation demonstrated superiority of FOLFIRINOX (bolus and infusional 5-fluorouracil (FU), irinotecan, oxaliplatin) in patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤1. Recently, three studies were presented in abstract form, comparing gemcitabine/S-1 (GS) to gemcitabine. S-1 is a mixture of tegafur (an oral 5-FU prodrug), a dihydropyrimidine dehydrogenase inhibitor and an agent designed to reduce the gastrointestinal toxicity of 5-FU. All three trials demonstrated significant improvements in progression-free survival (PFS) while one study also showed a statistically significant improvement in overall survival (OS). Methods: We performed a meta-analysis of the three trials. Results: Seven hundred and seventy patients were randomized to receive GS vs. gemcitabine; 75% had metastatic disease and 65% had an ECOG PS of 0. GS was associated with superior RR (hazard ratio (HR) 0.348, p=3.06×10^-7), PFS (HR 0.64, p=7.26×10^-9) and OS (HR 0.79, p=2.47×10^-2) compared to gemcitabine. Patients receiving GS were more likely to experience nausea, diarrhea, rash and stomatitis (mostly grade 1/2); neutropenic fever occurred in <2% of patients. One study demonstrated superior quality-of-life for GS. Conclusions: GS should be considered a first-line option for the treatment of advanced PC in Asian patients. This regimen should serve as the reference for future trials and comparison with FOLFIRINOX in patients with ECOG PS ≤1 is warranted.

Bevacizumab in combination with chemotherapy increases progression-free survival (PFS), but not overall survival when compared to chemotherapy alone in the treatment of metastatic breast cancer (MBC). Recently in November, 2011 the Food and drug administration revoked approval of bevacizumab in combination with paclitaxel for the treatment of MBC. The European Medicines Agency, in contrast, maintained its approval of bevacizumab in MBC. While neither agency considers health economics in their decision-making process, one of the greatest challenges in oncology practice today is to reconcile hard-won small incremental clinical benefits with exponentially rising costs. To inform policy-makers in the US, this study aimed to assess the cost-effectiveness of bevacizumab/paclitaxel in MBC, from a payer perspective. We created a decision analytical model using efficacy and adverse events data from the ECOG 2100 trial. Health utilities were derived from available literature. Costs were obtained from the Center for Medicare Services Drug Payment Table and Physician Fee Schedule and are represented in 2010 US dollars. Quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER) were calculated. Sensitivity analyses were performed. Bevacizumab added 0.49 years of PFS and 0.135 QALY with an incremental cost of $100,300, and therefore a cost of $204,000 per year of PFS gained and an ICER of $745,000 per QALY. The main drivers of the model were drug acquisition cost, PFS, and health utility values. Using a threshold of $150,000/QALY, drug price would have to be reduced by nearly 80% or alternatively PFS increased by 10 months to make bevacizumab cost-effective. The results of the model were robust in sensitivity analyses. Bevacizumab plus paclitaxel is not cost-effective in treating MBC. Value-based pricing and the development of biomarkers to improve patient selection are needed to better define the role of the drug in this population.

Previous Medicare payment changes have led to changes in the way oncology practices are structured. Understanding the complexities of oncology care is thus key for the success of newer reimbursement methods.

BACKGROUND: Epidermal growth factor receptor (EGFR) testing and first‐line therapy with gefitinib for patients with activating mutations is quickly becoming the standard option for the treatment of advanced lung adenocarcinoma. Yet, to date, little is known about the cost‐effectiveness of this approach. METHODS: A decision‐analytic model was developed to determine the cost‐effectiveness of EGFR testing and first‐line treatment with gefitinib for those patients who harbor activating mutations versus standard care, which includes first‐line treatment with chemotherapy followed by gefitinib as second‐line treatment. The model uses clinical and outcomes data from randomized clinical trials and societal costs from Singapore cancer centers. Health effects were expressed as quality‐adjusted life‐years. All costs and cost‐effectiveness ratios were expressed in 2010 Singapore dollars. Sensitivity and different scenarios analyses were conducted. RESULTS: EGFR testing and first‐line treatment with gefitinib is a dominant strategy (with lower costs and greater effectiveness) compared with standard care. Because the primary savings result from not providing gefitinib to those who are not likely to benefit, this finding holds regardless of the prevalence of activating mutations. In a secondary analysis, first‐line treatment with gefitinib was also dominant when compared with first‐line chemotherapy in patients with activating EGFR mutations. CONCLUSIONS: This strategy can be considered a new standard of care and should be of great interest for health care payers and decision makers in an era in which our greatest challenge is to balance hard‐won and incremental, yet small, improvements in patient outcomes with exponentially rising costs. Cancer 2012;. © 2011 American Cancer Society.