Plinabulin regimen extends OS in advanced EGFR wild-type non-small cell lung cancer
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The addition of plinabulin to docetaxel during second- or third-line treatment significantly extended OS for patients with EGFR wild-type non-small cell lung cancer, according to topline data released by the agent’s manufacturer.
Results of the randomized, phase 3 DUBLIN-3 registrational trial also showed the combination of plinabulin (BeyondSpring) — a first-in-class, selective immunomodulating microtubule-binding agent — and docetaxel significantly improved overall response rate and PFS, as well as OS at 24 months and 36 months, among this patient population.
In addition, researchers reported a significant reduction in incidence of grade 4 neutropenia.
“The treatment of second- and third-line NSCLC, especially with EGFR wild-type where tyrosine kinase inhibitors do not work, is an area of severe unmet medical need,” Trevor M. Feinstein, MD, of Piedmont Cancer Institute and principal investigator for DUBLIN-3, said in a BeyondSpring-issued press release. “In DUBLIN-3, a prolonged survival benefit, characterized by a long-tailed OS curve, was observed with plinabulin that represents an immune-associated anticancer benefit. The opportunity that plinabulin offers to these patients is not only to live longer, but also with significantly reduced severe neutropenia, which are both meaningful for these very sick patients.”
The trial enrolled 559 patients with EGFR wild-type NSCLC and measurable lung lesions. Patients received a 21-day cycle of 75 mg/m2 docetaxel via IV on day 1 alone (n = 281) or with 30 mg/m2 plinabulin on days 1 and 8 (n = 278).
OS served as the primary endpoint. Secondary endpoints included ORR, PFS, incidence of grade 4 neutropenia, and 24-, 36-, and 48-month OS rates.
Results showed the combination met the primary endpoint of increased OS (mean OS, P = .03; OS log rank, P < .04). Researchers also observed improvements in ORR (P < .03) and PFS (P < .01), a lower rate of grade 4 neutropenia at day 8 of cycle 1 (27.8% vs. 5.3%; P < .0001), and higher rates of OS at 24 months (22.1% vs. 12.5%; P < .01) and 36 months ( 11.7% vs. 5.3%; P < .04) with the combination vs. docetaxel alone.
Safety data revealed no unexpected concerns related to adverse events.
“It is especially gratifying to see the doubling of 24- and 36-month OS rate with a favorable safety profile in the plinabulin combination arm; this profile not only significantly advances [care of patients with NSCLC], but also signals plinabulin’s profound immune anticancer benefit,” Yan Sun, MD, chairman of National Comprehensive Cancer Network guidelines of NSCLC in China and director of GCP Center at Cancer Hospital of Chinese Academy of Medical Sciences, said in the press release. “The success of the DUBLIN-3 study is the gateway of plinabulin into multiple tumor indications within [immuno-oncology] combinations.”
BeyondSpring intends to seek FDA approval for the combination in NSCLC based on these results, with submission of a new drug application planned for the first half of 2022. Complete data will be presented at an upcoming medical meeting.
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