NET-02 final results: A randomised, phase II trial of liposomal irinotecan (nal-IRI)/5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line (2L) therapy in patients (pts) with progressive poorly differentiated extrapulmonary neuroendocrine carcinoma (PD-EP-NEC).

Abstract

646 Background: As demonstrated in the primary analysis of NET-02, nal-IRI/5-FU/folinic acid, but not docetaxel, met the primary endpoint of 6 month (mo) progression-free survival (PFS) rate in pts with progressive PD-EP-NEC. Here, the final results are presented. Methods: This was a multi-centre, randomised (1:1), phase II trial of IV nal-IRI (70mg/m2 free base)/5-FU (2400 mg/m2)/folinic acid, Q14 days (ARM A), or IV docetaxel (75mg/m2), Q21 days (ARM B), as 2L therapy in pts with progressive PD-EP-NEC, aimed at selecting a treatment for continuation to a phase III trial. On disease progression, pts in both arms could receive further systemic treatment as recommended by their physicians. Primary endpoint was 6 mo PFS rate; 80% power to demonstrate the one-sided 95% confidence interval (CI) of the 6 mo PFS rate excluded 15%, if the true rate was ≥30% (required level of efficacy); a rate of <15% would give grounds for rejection (additional selection criteria: toxicity and quality of life (QoL)). Intention was to show that regimens were sufficiently active, but not to assess superiority of one regimen over the other. Secondary endpoints included objective response rate (ORR), PFS, overall survival (OS), toxicity, QoL (European Organisation for Research and Treatment of Cancer QLQ C30 and GINET21) and translational end-points. Results: Of 58 pts in 15 UK centres (Nov 18-Dec 21), 29 in ARM A (2 pts excluded for efficacy analysis: well-differentiated grade 3 (G3) neuroendocrine tumour and goblet cell adenocarcinoma), 29 in ARM B. Eight pts in both arms (27.6% each) received subsequent chemotherapy. Fifty-four pts (93%) have died; the primary end-point of 6-mo PFS rate was met in ARM A; ORR, median PFS and OS are also presented. Adverse events ≥ G3 occurred in 51.7% and 55.2% in ARM A and B with 1 and 6 discontinuations due to toxicity in ARM A and B, respectively. Health-related QoL was maintained (C30 functional scales & global health status remained stable pre-progression) and potentially improved (sustained improvement in role functioning) with nal-IRI/5-FU/folinic acid, but not docetaxel (all C30 functional scales & global health status worsened between baseline and week 18, and treatment-related symptoms also worsened in GINET21). Translational analysis is on-going. Conclusions: nal-IRI/5-FU warrants further evaluation in pts with PD-EP-NEC, with the results highlighting that conduct of randomised trials in this disease group of unmet need is possible and safe. Clinical trial information: NCT03837977 . [Table: see text]