Testing alternative schedules of adjuvant immune checkpoint blockers – The need for well-designed clinical trials

Immune checkpoint blockers (ICB) have transformed the treatment landscape of many advanced cancers, and attention naturally shifts to the adjuvant setting. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved four anti-PD-(L)1 antibodies (atezolizumab, durvalumab, nivolumab, and pembrolizumab) in a total of nine adjuvant indications, as of October 2022 (Table 1) . The cost of these drugs is in excess of $150,000 a year for all ICB listed (e.g. US list price of 200 mg pembrolizumab is $20,948). Table 1List of approved immune checkpoint blockers as (neo)adjuvant treatment as of October 2022. Drug Cancer FDA approval EMA approval Dose and schedule on the drug's label (number of administration) First schedule Other schedule(s) Pembrolizumab Melanoma Yes Yes 200 mg Q3W (18) 400 mg Q6W (9) Pembrolizumab TNBC Yes Yes 200 mg Q3W (8 a neoadjuvant; NSCLC: non-small cell lung cancer, RCC; renal cell carcinoma, TNBC: triple-negative breast cancer. +9) 400 mg Q6W (4 a neoadjuvant; NSCLC: non-small cell lung cancer, RCC; renal cell carcinoma, TNBC: triple-negative breast cancer. +4) Pembrolizumab RCC Yes Yes 200 mg Q3W (18) 400 mg Q6W (9) Nivolumab Melanoma Yes Yes 240 mg Q2W (26) 480 mg Q4W (13) Nivolumab Urothelial Yes Yes 240 mg Q2W (26) 480 Mg Q4W (13) Nivolumab Oesophageal Yes Yes 240 mg Q2W (26) 480 mg Q4W (13) Nivolumab NSCLC Yes Yes 360 mg Q3W (3 a neoadjuvant; NSCLC: non-small cell lung cancer, RCC; renal cell carcinoma, TNBC: triple-negative breast cancer. ) / Atezolizumab NSCLC Yes Yes 840 mg Q2W (26) 1200 mg Q3W (17) or 1680 mg Q4W (13) Durvalumab NSCLC Yes Yes 10 mg/kg Q2W (26) 1500 mg Q4W (13) a neoadjuvant; NSCLC: non-small cell lung cancer, RCC; renal cell carcinoma, TNBC: triple-negative breast cancer. Open table in a new tab