KEY TAKEAWAYS
- The DUBLIN-3 phase 3 trial aimed to evaluate the efficacy and safety of plinabulin plus docetaxel for patients with advanced EGFR wild-type NSCLC.
- The primary endpoint was OS.
- Plinabulin plus docetaxel improved outcomes and reduced severe neutropenia in patients with advanced EGFR wild-type NSCLC.
Patients with advanced/metastatic non-small-cell lung cancer (NSCLC) lacking driver mutations, who experience disease progression following platinum-based therapy, face limited therapeutic options and a poor prognosis. Effective and tolerable treatment strategies are urgently needed for this patient population.
Trevor Feinstein and the team aimed to investigate the efficacy and safety of plinabulin, a novel microtubule-targeting agent, in combination with docetaxel, compared to docetaxel alone, in patients with advanced EGFR wild-type NSCLC who progressed after first-line platinum-based therapy.
DUBLIN-3 was a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial conducted across 58 medical centers in the US, China, and Australia. Patients were randomly assigned (1:1) to receive either docetaxel (75 mg/m2) on Day 1 plus plinabulin (30 mg/m2) or placebo on Days 1 and 8 of a 21-day cycle.
Treatment continued until disease progression, unacceptable toxicity, withdrawal, or death. The primary endpoint was overall survival (OS) in the intent-to-treat (ITT) population. Secondary endpoints included objective response rate (ORR) and progression-free survival (PFS).
Between November 30, 2015, and January 6, 2021, 559 patients were enrolled. Plinabulin plus docetaxel significantly improved OS compared with docetaxel alone (median OS 10.5 months vs. 9.4 months; HR 0.82, 95% CI 0.68-0.99, P=0.0399).
With additional follow-up, the OS benefit was maintained (median OS 10.8 vs. 9.3 months, HR=0.81, P=0.0027). Plinabulin also significantly improved PFS (median PFS 3.3 months vs. 2.8 months; HR 0.79; 95% CI 0.66-0.96; P=0.0174) and ORR (14.0% vs. 8.5%; difference 5.5%, 95% CI 0.26-10.72; P=0.0404).
The safety profile of the combination was manageable, with a higher incidence of Grade 3/4 gastrointestinal disorders and transient Grade 3 hypertension in the plinabulin arm.
The study concluded that plinabulin plus docetaxel significantly improved OS, PFS, and ORR in patients with advanced EGFR wild-type NSCLC who progressed after platinum-based therapy. The combination was well-tolerated with a manageable safety profile, suggesting it may represent a new standard of care for this population.
The trial was sponsored by BeyondSpring Pharmaceuticals Inc.
Source: https://cattendee.abstractsonline.com/meeting/20598/presentation/725
Clinical Trial: https://clinicaltrials.gov/study/NCT02504489
Feinstein T, Han B, Shi Y, et al. (2024). “Plinabulin/Docetaxel vs. Docetaxel in 2L/3L NSCLC after Platinum Regimens (DUBLIN-3): A Phase 3 Randomized Controlled Trial.” Presented at: World Conference on Lung Cancer (WCLC); September 9, 2024; Singapore.
