Anticancer drugs approved by the Food and Drug Administration for gastrointestinal malignancies: Clinical benefit and price considerations

Abstract

Background The cost of new anticancer drugs is rising. We aimed to assess the clinical benefit and price of anti‐cancer drugs approved by the US Food and Drug Administration (FDA) for advanced gastrointestinal cancers. Methods Drugs approved between 2006 and 2017 for advanced GI malignancies were identified from FDA.gov, and their updated supporting trial data were searched. Incremental clinical benefit was quantified by using ESMO Magnitude of Clinical Benefit Scale version 1.1 (grade 0‐5) and ASCO Value Framework version 2 (score range −20 to 180). Higher scores indicate larger net benefit, and substantial benefit was defined as score 4 or 5 by the European Society for Medical Oncology (ESMO). The Micromedex REDBOOK was used to estimate the monthly average wholesale price (AWP) and total drug price (TDP) over the median treatment duration per patient. Clinical benefit, AWP and TDP of each drug class were assessed. Results In total, 16 GI cancer drugs received FDA approval for 24 indications, including five monoclonal antibodies (mAbs), five oral targeted therapies (TT), two immunotherapeutics (IO), three cytotoxic chemotherapies (CT), and one recombinant fusion protein (aflibercept). Most supporting trials (82%) reported overall survival benefit of less than 3 months and no significant improvement in quality of life. Only five agents (including one TT and one IO) with 21% the of approved indications met the ESMO's threshold of substantial clinical benefit. Median incremental benefit scores of TT and IO were comparable to other drug classes. However their median TDP was much higher at $153 402 and $98 208, respectively, compared to $30 330 USD per patient for CT. The estimated TDP did not correlate with clinical benefit scores. Conclusion Most FDA–approved gastrointestinal cancer drugs do not meet the ESMO threshold of substantial clinical benefit. TT and IO are estimated to carry significant drug costs, and further cost analysis of these drugs is urgently needed.

Assessment of Food and Drug Administration– and European Medicines Agency–Approved Systemic Oncology Therapies and Clinically Meaningful Improvements in Quality of Life

“…Despite the in-depth review of data by the FDA and EMA for drugs seeking regulatory approval, the majority of approvals are based on survival end points, with limited published QOL evidence available at the time of approval. 20,21 While 40% of FDA and 58% of EMA approved indications evaluated in [24][25][26][27] Of note, Saluja et al 27 suggest that such marginal improvements in overall clinical benefit as measured by the ASCO-VF and ESMO-MCBS are accompanied by substantial increases in cost over time. Our findings serve to extend previously published work suggesting that, when considering QOL alone, a fairly limited subset of recently approved oncology drugs achieve differences in QOL that can be considered clinically meaningful.…”

“… 23 A plethora of previously published work suggests that, overall, recently approved oncology drugs demonstrate limited clinically meaningful benefits based on total ASCO-VF and ESMO-MCBS scores. 24 , 25 , 26 , 27 Of note, Saluja et al 27 suggest that such marginal improvements in overall clinical benefit as measured by the ASCO-VF and ESMO-MCBS are accompanied by substantial increases in cost over time. Our findings serve to extend previously published work suggesting that, when considering QOL alone, a fairly limited subset of recently approved oncology drugs achieve differences in QOL that can be considered clinically meaningful.…”

Economic challenges of oncological diseases’ pharmacotherapy

“…Итальянские эксперты, проанализировавшие 30 новых противоопухолевых ЛС (зарегистрированы по 35 показаниям), одобренных в Евросоюзе в 2010-2016 гг., и стоимость которых возмещается в Италии, также пришли к заключению, что цены на эти препараты не отражают их терапевтическую пользу [33]. Аналогичное заключение было сделано и в недавно опубликованном анализе ЛС, зарегистрированных в США для лечения злокачественных новообразований ЖКТ [34].…”

“…Одним из наиболее эффективных способов снижения стоимости лекарственной терапии является применение воспроизведенных препаратов [34]. Цены на воспроизведенные препараты могут колебаться в широких пределах, составляя от ≤10 до 80-90% от таковой оригинатора [57] и в значительной степени определяются политикой ценообразования в конкретной стране [58].…”

Trends in Drug Costs and Overall Survival in Patients with Metastatic Non-small Cell Lung Cancer in The Netherlands Diagnosed from 2008 Through 2014

“…More recently, immunotherapeutic agents directed on the programmed cell death-1 (PD-1) receptor or its ligand PD-L1 have demonstrated a broader benefit and durable responses in NSCLC [2]. However, concern is growing that the magnitude of the survival benefit from these new anticancer therapies does not justify its high prices [3][4][5][6]. Moreover, the benefits of new treatments might not be clinically meaningful to patients [7].…”