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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Friday, March 22, 2024
In the search for effective treatments for patients with metastatic non–small cell lung cancer (NSCLC) whose disease has progressed on checkpoint inhibitors, a phase II study was conducted by Angel Qin, MD, of the University of Michigan Rogel Cancer Center, Ann Arbor, and colleagues to assess the efficacy of combining pevonedistat, an inhibitor of the NEDD8-activating enzyme, with docetaxel. This study, published in Clinical Lung Cancer, enrolled 31 patients with relapsed or refractory stage IV NSCLC. Pevonedistat acts by inhibiting neddylation, a process necessary for the activation of Cullin-RING ligases, which are overactivated in NSCLC. Preclinical studies indicated antitumor activity when pevonedistat was combined with docetaxel. The primary endpoint of the study was the objective response rate.
The combination treatment demonstrated a meaningful objective response rate of 22%, with one complete response and five partial responses observed among the patients. The median progression-free survival was 4.1 months, and the median overall survival was 13.2 months. Although there were significant adverse events, with grade ≥ 3 adverse events occurring in 53% of patients, including neutropenia and AST/ALT elevation, no grade 5 toxicities were reported. One patient was withdrawn from the study because of a grade 4 transaminase elevation.
These results suggest that the combination of docetaxel and pevonedistat is both safe and effective in patients with relapsed NSCLC. The study findings highlight the potential of targeting the neddylation pathway as an antitumor strategy and support further investigation into this approach. Despite the challenges posed by adverse events, the observed objective response rate and survival outcomes warrant consideration of this combination therapy as a treatment option for patients whose disease has progressed on checkpoint inhibitors.
Disclosure: The study authors reported no conflicts of interest.
