The impact of PD-L1 on survival and value of the immune check point inhibitors in non-small-cell lung cancer; proposal, policies and perspective

Abstract

Background: The impact of programmed death receptor-ligand1 (PD-L1) on costs and value of the immune check point inhibitors (ICPI) has received minimal attention. Objectives: 1- Design a sliding scale to grade survival in 2nd-line non-small-cell lung cancer (NSCLC). 2- Compare costs and value of Nivolumab (Nivo), Atezolizumab (Atezo) and Pembrolizumab (Pembro) vs. Docetaxel (Doc). Methods: Previously reported median overall survival (OS) and prices posted by parent company were utilized. The OS gains over controls in days were graded (gr) from A+ to D. Docetaxel costs were calculated for 6-12 cycles and the ICPI for 1 year. Adverse events treatment costs (AEsTC) were reported separately. The cost/life-year gain (C/LYG) was computed as drug yearly-cost/OS gain over control in days × 360 days. The relative value of the ICPI were expressed as $100,000/C/LYG. Results: Costs of Doc 6 cycles were $23,868, OS/gr 87/C, AEs gr 3/4 > 20%, AEsTC $1978 and 6- 12 cycle C/LYG $98,764 -$197,528. Nivo, Atezo and Pembro gr 3/4 were < 20% at average costs of $1480. In non-squamous NSCLC, Nivo demonstrated OS/g 84/C and C/LYG $558,326 as compared with 264/A and $177,645 in PD-L1 > 10%. Atezolizumab OS/g were 87/B and C/LYG $551,407 improving in enriched PD-L1 to 162/A and $332,020 respectively. Pembrolizumab in PD-L1 > 1.0% demonstrated OS/g 57/C and C/LYG $659,059 improving in > 50% PD-L1 to 201/A and $186,897. PD-L1 enrichment increased RV of Nivo from 0.18 to 0.56, Atezo from 0.16 to 0.66 and Pembro from 0.15 to 0.53. Conclusions: Simplified methodology to grade OS and weigh value of anticancer drugs was proposed. In 2nd-line non-squamous NSCLC, value of Doc, Nivo, Atezo and Pembro regardless of PDL-1 expression were limited and modest. Enrichment of PD-L1 resulted in unprecedented OS, improved grades and enhanced value at seemingly justifiable costs.