Low-Dose Anti-PD(L)1 for the Treatment of Solid Malignancies

JCO Glob Oncol. 2024 Nov:10:e2400122. doi: 10.1200/GO.24.00122. Epub 2024 Nov 21.

Abstract

Purpose: Mounting data suggest that lower doses of anti-PD(L)1 agents can be as efficacious as label-approved doses at a fraction of its cost. We compare the outcomes of patients treated with low-dose (LD) and with conventional-dose (CD) anti-PD(L)1 agents.

Methods: This observational study evaluates the outcomes of patients with solid malignancies treated with anti-PD(L)1 agents (LD or CD) at Hospital de Base, Brazil. Patients were classified as receiving LD if the dose administered in the first cycle was below the label-approved dose. Efficacy outcomes, including best clinical overall response rate (cORR), clinical progression-free survival (cPFS), and overall survival (OS), were evaluated.

Results: From January 2020 to May 2023, 71 patients were included: 49 (69%) with LD and 22 (31%) with CD agents. The most frequent tumor sites were the lung (41% LD, 22.9% CD) and skin (melanoma; 24.6% LD, 50% CD). Most of the patients were treated with pembrolizumab (65% LD and 72% CD). The mean dose of pembrolizumab was 95.3 mg (1.5 mg/kg) in LD and 168.7 mg (2.12 mg/kg) in CD groups, once a day, q21d (every 21 days). After a median follow-up of 10.9 months, there were no significant differences between LD versus CD in cORR (38.1% v 35.2%, P = .31), cPFS (5.3 m v 7 m, P = .36), and OS (12.8 m v not reached, P = .17). A subgroup analysis with patients receiving pembrolizumab was performed, and similar results were obtained.

Conclusion: Our study found no differences in cORR, cPFS, and OS between patients treated with LD and CD anti-PD(L)1. LD anti-PD(L)1 could be an alternative to promote accessibility, which warrants further investigation in randomized trials.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • B7-H1 Antigen / antagonists & inhibitors
  • Brazil
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immune Checkpoint Inhibitors / therapeutic use
  • Male
  • Middle Aged
  • Neoplasms* / drug therapy
  • Neoplasms* / immunology
  • Neoplasms* / mortality
  • Progression-Free Survival

Substances

  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen
  • Immune Checkpoint Inhibitors
  • pembrolizumab
  • CD274 protein, human