Efficacy and Safety of Ultra-Low-Dose Immunotherapy in Relapsed Refractory Solid Tumors: Phase III Superiority Randomized Trial (DELII)
Abstract
PURPOSE Immune checkpoint inhibitors (ICIs) achieve sufficient receptor occupancy at much lower than standard approved doses. We hypothesized that ultra-low-dose nivolumab would retain clinical efficacy. PATIENTS AND METHODS In this phase III randomized superiority trial, patients with advanced solid tumors (Eastern Cooperative Oncology Group 0-1) and progression on ≥1 prior line of systemic therapy were randomly assigned 1:1 to ultra-low-dose nivolumab (20 mg intravenously once every 2 weeks) or standard chemotherapy (docetaxel or paclitaxel, as per tumor type). Treatment continued until progression or intolerable toxicity. The primary end point was overall survival (OS). RESULTS From June 2020 to February 2024, we enrolled 500 patients: 250 per arm; 52% had head and neck and 36% lung cancers. The median number of prior lines of therapy was 1 (range, 1-8); 29% had received ≥2 prior lines. Median OS was significantly longer with ultra-low-dose nivolumab: 5.88 months (95% CI, 4.99 to 7.13) versus 4.70 months (95% CI, 3.91 to 5.65; hazard ratio [HR], 0.80 [95% CI, 0.66 to 0.97]; P = .022). One-year OS was 27.3% versus 16.9%. Median progression-free survival was similar: 2.04 months (95% CI, 2.00 to 2.10) with ultra-low-dose nivolumab and 2.09 months (95% CI, 2.04 to 2.17) with chemotherapy (HR, 1.03 [95% CI, 0.86 to 1.23]; P = .77). Grade ≥3 treatment-related adverse events were less frequent with ultra-low-dose nivolumab (42.5% v 60.8%; P < .001). Quality of life (QoL) was significantly better with ultra-low-dose nivolumab. CONCLUSION Ultra-low-dose nivolumab significantly improves OS versus chemotherapy in pretreated solid tumors, with fewer severe toxicities and better QoL. These findings support re-evaluation of ICI dosing strategies and may enhance global access.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (32)
Vanita Noronha
Kumar Prabhash, MD, DM, MBBS, Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India, Department of Medical Oncology, Homi Bhabha Cancer Hospital and Research Centre, Muzaffarpur, India; Vanita Noronha, MD, DM, MBBS, Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India; Akash Pawar, MSc, Department of Statistics, Advanced Centre for Treatment, Research and Education in Cancer, Homi Bhabha National Institute (HBNI), Mumbai, India, Ankush Shetake, MSc, Department of Statistics, Homi Bhabha Cancer Hospital and Research Centre, Muzaffarpur, India; and Rajendra Badwe, MS, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
Vijay Patil
61P.D. Hinduja Hospital, Mumbai, India
Nandini Menon
Tata Memorial Hospital, Mumbai, India
Minit Shah
Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
Vikas Ostwal
Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
Anant Ramaswamy
Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
Prabhat Bhargava
Srushti Shah
Tata Memorial Centre, Mumbai, India
Kavita Nawale
Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
Ankush Shetake
Kumar Prabhash, MD, DM, MBBS, Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India, Department of Medical Oncology, Homi Bhabha Cancer Hospital and Research Centre, Muzaffarpur, India; Vanita Noronha, MD, DM, MBBS, Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India; Akash Pawar, MSc, Department of Statistics, Advanced Centre for Treatment, Research and Education in Cancer, Homi Bhabha National Institute (HBNI), Mumbai, India, Ankush Shetake, MSc, Department of Statistics, Homi Bhabha Cancer Hospital and Research Centre, Muzaffarpur, India; and Rajendra Badwe, MS, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
Vijayalakshmi Mathrudev
Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
Laxman Sahu
Tata Memorial Hospital, Mumbai, India
Shreya Mehta
Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
Charushila Deshmukh
Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
Savita Gaikwad
Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
Shital Chavan
Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
Ravi Narayan
Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
Ravi Ingale
Gunvati Jagan Nath Kapoor Foundation, Mumbai, India
Sachin Dhumal
Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
Rajiv Kumar Kaushal
Trupti Pai
Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
Nilendu Purandare
Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
Amit Janu
Tata Memorial Centre, Mumbai, Maharashtra, India
Nivedita Chakrabarty
ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
Arpita Sahu
Tata Memorial Centre, Mumbai, India
Purvi Haria
Department of Radiodiagnosis, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
Arvind Vaidyanathan
Tata Memorial Centre, Mumbai, India
Mehak Trikha
Tata Memorial Hospital, Mumbai, India
Sandeep Gedela
Tata Memorial Hospital, Mumbai, India
Shripad Banavali
2Tata Memorial Hospital, Tata Memorial Centre, Mumbai, Pediatric Oncology, Mumbai, India
Rajendra A. Badwe
Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
Kumar Prabhash
Department of Medical Oncology, Division of Adult Solid Tumor Oncology, Tata Memorial Hospital, Mumbai, India