Efficacy and Safety of Low-Dose Versus Standard-Dose Immunotherapy in Advanced Solid Tumours: A Retrospective Real-World Study From a Resource-Constrained Setting.

Introduction Immunotherapy (IO) has revolutionised cancer treatment but is fairly expensive. This has prompted interest in the use of low-dose (LD) IO and is an area of active research. This study retrospectively evaluates the efficacy, safety, and survival outcomes of LD and regular-dose (RD) IO in advanced malignancies.  Methods A total of 53 patients with advanced (n = 2) or metastatic (n = 51) solid malignancies received IO between November 2021 and January 2024 at a tertiary care centre in Northern India. Patients received either LD (n = 42) or RD (n = 11) IO regimens, alone or in combination with other therapies. Treatment outcomes were assessed using the Immune-modified Response Evaluation Criteria in Solid Tumors (imRECIST) criteria, including progression-free survival (PFS), overall survival (OS), and toxicity profiles. Results The overall response rate (ORR) was 52.3% in the LD group and 54.5% in the RD group. Clinical benefit rates (CBR) were 61.9% and 54.5%, respectively. Median PFS was 7.97 months (LD) versus 8.73 months (RD), and median OS was 13.26 months (LD) versus 9.6 months (RD). Log-rank comparison did not reach statistical significance for either PFS or OS. As the RD cohort comprised only 11 cases, the study was not powered for comparative inference, and the numerically similar outcomes between groups should not be interpreted as evidence of equivalence. Durable complete responses (CRs) exceeding one year were observed in bladder, renal, and triple-negative breast cancers with LD. While favourable responses were also seen in other cancers across both cohorts, Grade ≥3 toxicities occurred in 2 of 42 patients (4.8%) in the LD group and 2 of 11 patients (18.2%) in the RD group and were manageable in both cohorts. Conclusions LD IO demonstrated good efficacy and safety across multiple tumour types in the real world, especially for malignancies such as bladder, renal, breast, and certain gastrointestinal and head and neck cancers. These findings support the feasibility of LD IO in resource-constrained settings and provide a preliminary rationale for adequately powered prospective studies to formally evaluate dose optimisation strategies in IO.