Low-dose anti-PD-(L)1 inhibitor strategies: A systematic review.

Abstract

1526 Background: Immune checkpoint inhibitors (ICIs) targeting the PD-(L)1 pathway have revolutionized cancer therapy, but their high costs significantly limit accessibility, particularly in low- and middle-income countries (LMICs). Low-dose regimens may offer a viable solution to this challenge. This systematic review analysed study designs, dosing strategies, clinical outcomes, and potential cost savings of low-dose ICIs. Methods: A PRISMA/EQUATOR compliant systematic search of WebOfScience, Cochrane Central Register of Clinical Trials, ASCO and ESMO conference databases was conducted until October 10 th , 2024. Studies investigating reduced-dose anti-PD(L)1 from those FDA/EMA-approved regimens were included. Data were categorized by dose and country income level. Results: From 1,751 records, 25 studies (4 clinical trials, 21 observational studies) involving 1,793 participants met inclusion criteria, with 1,202 receiving low-dose ICIs. Two studies used non-inferiority designs, and 21 evaluated participants across multiple treatment lines. The population had a median age of 53.1 years (range 19–84), 26% female, 88% with advanced disease, and 9% ECOG ≥2. Most studies were conducted in Asia (81.4%, n = 1,459), with head and neck (22.8%, n = 409) and non-small cell lung cancers (17.3%, n = 311) being most studied. 48% studies were from LMICs, 44% from high-income countries (HIC), and 8% from upper middle-income countries (UMIC). India contributed the most (studies, k = 12, 839 participants). Nivo ( k = 21), pembro ( k = 6) and atezo ( k = 1) were assessed. The most common regimens were Nivo40mg Q2W ( k = 7), Nivo20mg Q3W ( k = 6) and Nivo20mg Q2W ( k = 5) [Table 1]. A radiological response rate between 5-75% was noted when low-dose ICI was used as monotherapy ( k = 10). High variability in participant selection and interventions restricts further conclusions about efficacy and safety. The median projected savings were 83.3% (25–99.40%), with ≥70% savings in half of the studies. Conclusions: This review described the use of low-dose anti-PD(L)1 drugs, especially in healthcare settings with limited resources, highlighting radiological responses observed with monotherapy. Non-inferiority or near-equivalence randomized clinical trials will be helpful in establishing their clinical validity. Tumor type(origin from participants assessed) HNSCCn=409 NSCLC n=311 HCCn=93 RCC n=73 HL n=70 Multiple n=57 Melanoma n=56 Gastric/GEJ n=42 Gyne n=35 CCR n=30 Cervical n=20 Thymic n=6 LMIC 409 57 57 42 30 20 UMIC 23 6 HIC 311 93 16 47 56 35 Number of studies (k) assessing each dose per tumor k: 6 k: 4 k: 2 k: 2 k: 3 k: 2 k: 1 k: 1 n: 1 n: 1 n: 1 n: 1 Nivo 0.3 mg/Kg Q2W 1 Nivo 10 mg Q2W 2 1 Nivo 10 mg Q8W 1 Nivo 20 mg Q2W 1 2 1 1 Nivo 20 mg Q3W 3 1 1 Nivo 40 mg Q2W 1 3 2 1 Nivo 40 mg Q3W 3 1 1 1 Nivo 40 mg Q4W 1 Nivo 80 mg Q4W 1 Nivo 100 mg Q2W 1 1 1 Nivo 100 mg Q3W 1 Nivo 100 mg Q4W 1 Nivo 140 mg Q2W 1 1 Pembro 1 mg/Kg Q3W 1 Pembro 1 mg/Kg Q6W 1 Pembro 50 mg Q3W 1 Pembro 100 mg Q3W 3 1 1 Pembro 300 mg Q6W 1 Atezo 1 mg/Kg Q3W 1