In an Indian single-center phase III trial (DELII) reported in the Journal of Clinical Oncology, Noronha et al found that “ultra–low-dose” immune checkpoint inhibitor therapy with the PD-1 inhibitor nivolumab was associated with improved overall survival vs standard chemotherapy among patients with relapsed or refractory solid tumors.
Study Details
In the open-label trial, 500 patients with solid tumors with disease progression on one or more prior line(s) of systemic therapy were enrolled at Tata Memorial Hospital, Mumbai, between June 2020 and February 2024. Patients were randomly assigned to receive nivolumab at 20 mg every 2 weeks or standard chemotherapy with docetaxel or paclitaxel according to tumor type. Most patients had head and neck cancer (52%) or lung cancer (36%) as primary sites; metastatic disease was present in 53% of all patients. The median number of prior lines of therapy was one (range = 1–8), with 29% of patients receiving two or more prior lines. The primary endpoint of the trial was overall survival.
Key Findings
Median overall survival was 5.88 months (95% confidence interval [CI] = 4.99–7.13 months) in the nivolumab group vs 4.70 months (95% CI = 3.91–5.65 months) in the chemotherapy group (hazard ratio [HR] = 0.80, 95% CI = 0.66–0.97, P = .022); rates at 1 year were 27.3% vs 16.9%. Hazard ratios for overall survival were 0.86 (95% CI = 0.67–1.11) among patients with head and neck cancer and 0.77 (95% CI = 0.59–1.01) among those with other cancers. Median progression-free survival was 2.04 months (95% CI = 2.00–2.10 months) in the nivolumab group vs 2.09 months (95% CI = 2.04–2.17 months) in the chemotherapy group (HR = 1.03, 95% CI = 0.86–1.23, P = .77).
Grade ≥ 3 treatment-related adverse events occurred in 42.5% of patients in the nivolumab group vs 60.8% of those in the chemotherapy group (P < .001), most commonly hyponatremia in both groups (28.6% vs 40.5%). Global health status improved over time (P < .001) in both groups, with a better trajectory in the nivolumab group (P = .014).
The investigators concluded: “Ultra–low-dose nivolumab significantly improves [overall survival] vs chemotherapy in pretreated solid tumors, with fewer severe toxicities and better [quality of life]. These findings support re-evaluation of [immune checkpoint inhibitor] dosing strategies and may enhance global access.”
Kumar Prabhash, DM, MD, MBBS, of the Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was funded by the R. G. Manudhane Foundation for Excellence, Trilokchand Papriwal Trust, and Tata Memorial Hospital. For full disclosures of the study authors, visit ascopubs.org.
