The following is the summary of “NEPTUNE: Phase 3 Study of First-Line Durvalumab Plus Tremelimumab in Patients With Metastatic NSCLC” published in the January 2023 issue of Thoracic oncology by Castro, et al.
The NEPTUNE research compared first-line durvalumab and tremelimumab to chemotherapy for patients with metastatic non-small cell lung cancer (mNSCLC). Durvalumab (20 mg/kg every 4 weeks till progression)+ tremelimumab (1 mg/kg every 4 weeks for up to 4 doses) or standard chemotherapy was randomly assigned to eligible patients with EGFR and ALK wild-type mNSCLC (1:1). Tumors were divided into 2 groups based on the percentage of programmed death-ligand 1 (PD-L1) expression inside the tissue of the patient’s tumor. Patients with a blood tumor mutational burden (bTMB) of 20 mutations per megabase (mut/Mb) or above had OS set as the primary end point.
Patients with bTMB more than or equal to 20 mut/Mb had a secondary end aim of progression-free survival (PFS), whereas all treated patients had a secondary end point of safety and tolerability. 823 patients had been randomized (ITT) as of June 24, 2019; 512 (62%) were bTMB-evaluable, and 129 of 512 (25%) had bTMB more than or equivalent to 20 mut/Mb (durvalumab + tremelimumab [n=69]; chemotherapy [n=60]). Intention-to-treat analysis was performed with a focus on achieving balance in baseline characteristics. Durvalumab plus tremelimumab versus chemotherapy did not significantly improve overall survival (hazard ratio 0.71 [95% CI: 0.49-1.05; P=0.081]; median OS, 11.7 versus 9.1 months); hazard ratio for progression-free survival (PFS) was 0.77 (95% CI: 0.51-1.15; median PFS, 4.2 versus 5.1 months).
Treatment-related adverse events of grade 3 or 4 occurred at a rate of 20.7% (durvalumab plus tremelimumab) and 33.6% (alone) in the overall safety group (chemotherapy). The primary end point of the NEPTUNE trial, which compared (durvalumab + tremelimumab to chemotherapy for patients with mNSCLC and bTMB > or=20 mut/Mb), was not reached. Therapeutic activity was consistent with expectations based on molecular biology and prior investigations, despite the modified study design, which resulted in a small primary analysis sample.