Cost-effectiveness of RAS screening before monoclonal antibodies therapy in metastatic colorectal cancer based on FIRE3 Study

Abstract

The surprising results published by FIRE-3 revealed that the overall survival (OS) of RAS wild-type metastatic colorectal cancer (mCRC) patients treated with Cetuximab(Cmab) and FOLFIRI combination was prolonged to 33.1 months. The substantial increase in testing and treatment costs, however, impose a considerable health burden on patients and society. Hence the study was aimed to assess the cost-effectiveness of RAS screening before monoclonal antibodies (mAbs) therapy based on FIRE-3 study. Four groups were analyzed: group 1, patients with KRAS testing treated with Cmab and FOLFIRI; group 2, patients with RAS testing treated with Cmab and FOLFIRI; group 3, patients with KRAS testing treated with bevacizumab(Bmab) and FOLFIRI; group 4, patients with RAS testing treated with Bmab and FOLFIRI. A Markov model comprising 3 health states (progression-free survival, progressive disease and death) was built. The costs were calculated from a Chinese payer perspective, and survival was reported in quality-adjusted life-months (QALMs). Average total lifetime costs ranged from $104,682.44 (RAS-Bmab) to $136,867.44 (RAS-Cmab), while the survival gained varied from 16.88 QALMs in RAS-Bmab to 21.85 QALMs in RAS-Cmab. The cost per QALM was $6,263.86 for RAS-Cmab, $6,145.84 for KRAS-Bmab, $6,201.57 for RAS-Bmab and $6,960.70 for KRAS-Cmab respectively. The KRAS-Cmab strategy was dominated by the other 3 groups. The first-treatment cost of RAS-Cmab was the most influential one to the model. In all, the RAS screening prior to Cmab treatment in mCRC seems to be a cost-effective strategy in the time of monoclonal antibodies (mAbs) therapy with the most gained QALMs.

Do cancer biomarkers make targeted therapies cost-effective? A systematic review in metastatic colorectal cancer

“…Five studies showed cost-saving [ 41 – 45 ] compared to that of ‘no-testing’. Wen et al [ 32 ] evaluated cost-effectiveness of RAS screening prior to monoclonal antibodies and found that RAS testing before cetuximab is more cost-effective compared to KRAS-testing with cetuximab. After re-calculating their ICERs, we concluded that all strategies they used were well beyond the acceptable willingness to pay thresholds in China, but RAS testing appeared to be more favourable than KRAS testing for patients with mCRC.…”

“…Seven studies evaluated the cost-effectiveness of RAS testing and most of them found favourable results for RAS biomarker testing ( Table 2 ). Of these, two studies assessed the cost-effectiveness of RAS screening compared with that of KRAS testing with targeted therapies [ 32 , 36 ]. Both studies were performed from a Chinese health care system perspective and found that RAS testing was cost-effective compared to KRAS testing with cetuximab.…”

Cost-Effectiveness Analysis of First-Line FOLFIRI Combined With Cetuximab or Bevacizumab in Patients With RAS Wild-Type Left-Sided Metastatic Colorectal Cancer

“…[4][5][6][7]35 The best treatment decisions are driven by multiple factors, including drug costs, anticipated toxicities, and practice patterns, in addition to therapeutic effects. Recently, several studies in other countries have evaluated the cost-effectiveness of routine RAS screening in patients with mCRC [36][37][38] and Abbreviations: FOLFIRI, irinotecan, leucovorin, and fluorouracil; FOLFOX, oxaliplatin, leucovorin, and fluorouracil; ICER, incremental cost-effectiveness ratio; LY, life-year; QALY, quality-adjusted life-year; WTP, willingness-to-pay.…”

Pharmacoeconomic-guided choice of systemic chemotherapy in metastatic colorectal cancer patients

“…Однако данный вывод был сделан при сравнении результатов проспективных исследований эффективности добавления того или иного моноклонального антитела к химиотерапии без прямого проспективного сравнения эффективности моноклональных антител между собой [33]. В то же время при изолированном метастатическом поражении печени и «диком» типе гена KRAS в немецком исследовании цетуксимаб в комбинации с режимом FOLFIRI в 1-й линии оказался более эффективным по сравнению со схемой FOLFOX + бевацизумаб (ICER € 15 020 / LYG) [35].…”

“…• Авторы пришли к выводу, что комбинация цетуксимаба с химиотерапией при отсутствии мутаций в генах семейства RAS эффективнее сочетания с бевацизумабом не только клинически, но и экономически [35].…”