ABOUND.2L+: A randomized phase 2 study of nanoparticle albumin-bound paclitaxel with or without CC-486 as second-line treatment for advanced nonsquamous non-small cell lung cancer (NSCLC).

Abstract

BACKGROUND:

This randomized phase 2 trial compared the efficacy and safety of second-line nanoparticle albumin-bound paclitaxel (nab-paclitaxel) with or without the addition of CC-486 (an oral formulation of 5-azacytidine) in patients with advanced-stage, nonsquamous non-small cell lung cancer.

METHODS:

Patients were randomized to receive either nab-paclitaxel 100 mg/m2 on days 8 and 15 plus CC-486 200 mg daily on days 1 to 14 or single-agent nab-paclitaxel 100 mg/m2 on days 1 and 8, with both regimens administered every 21 days until tumor progression or unacceptable toxicity. The primary endpoint was progression-free survival. Secondary endpoints included the overall response rate, the disease control rate, and overall survival.

RESULTS:

Between January 2015 and August 2016, 161 patients were randomized (81 to the combination arm and 80 to the single-agent nab-paclitaxel arm). There was no benefit from the addition of CC-486 to nab-paclitaxel. The median progression-free survival was 3.2 months for the combination and 4.2 months for single-agent nab-paclitaxel (hazard ratio, 1.3; 95% confidence interval, 0.9-1.9). The median overall survival was 8.1 months in the combination arm and 17 months in the single-agent nab-paclitaxel arms (hazard ratio, 1.7; 95% confidence interval, 1.08-2.57). Grade 3 or greater treatment-related, emergent adverse events were reported by 40.5% of patients in the combination arm and by 31.6% of those in the single-agent nab-paclitaxel arm.

CONCLUSIONS:

Single-agent nab-paclitaxel was associated with promising outcomes and a tolerable safety profile as second-line treatment for patients with advanced-stage, nonsquamous non-small cell lung cancer. There was no benefit from the addition of CC-486 to nab-paclitaxel.

• Authors: Daniel Morgensztern, Manuel Cobo, Santiago Ponce Aix, Pieter E Postmus, Conrad R Lewanski, Jaafar Bennouna, Jürgen R Fischer, Oscar Juan-Vidal, David J Stewart, Gianpiero Fasola, Andrea Ardizzoni, Rafia Bhore, Marianne Wolfsteiner, Denis C Talbot, Teng Jin Ong, Ramaswamy Govindan, On Behalf Of The Abound L Investigators
• Journal: Cancer (Cancer) Vol. 124 Issue 24 Pg. 4667-4675 (12 15 2018) ISSN: 1097-0142 [Electronic] United States
• PMID: 30383906 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 American Cancer Society.

Chemical References

• 130-nm albumin-bound paclitaxel
• Albumins
• Antibodies, Monoclonal
• durvalumab
• Azacitidine
• Paclitaxel

Topics

• Administration, Oral
• Adult
• Aged
• Aged, 80 and over
• Albumins (administration & dosage, adverse effects)
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Azacitidine (administration & dosage, adverse effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Humans
• Lung Neoplasms (drug therapy)
• Male
• Middle Aged
• Paclitaxel (administration & dosage, adverse effects)
• Treatment Outcome