The ABOUND.2L+ trial tested the combination of nab-paclitaxel and CC-486 vs single-agent nab-paclitaxel in patients with advanced NSCLC.
Patients with advanced-stage nonsquamous non–small-cell lung cancer (NSCLC) had favorable results with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as a second-line therapy, according to results of a phase II trial. The addition of an oral formulation of 5-azacytidine known as CC-486 did not add any benefit.
Immune checkpoint inhibition is increasingly used in this patient population, and adding pembrolizumab to a platinum doublet regimen has been shown to be more effective than chemotherapy alone, but even with these new approaches the long-term results are limited. “Therefore, the vast majority of patients who receive an [immune checkpoint inhibitor], either as first-line treatment or in subsequent lines, eventually develop tumor progression and become eligible for subsequent chemotherapy,” wrote study authors led by Daniel Morgensztern, MD, of the Washington University School of Medicine in St. Louis.
The ABOUND.2L+ trial randomized 161 patients with advanced-stage nonsquamous NSCLC to receive either a combination of nab-paclitaxel and CC-486 (81 patients) or to single-agent nab-paclitaxel (80 patients). The median age in the two arms was 65 years and 63 years, respectively, and over 80% of the patients were white; the results were published in Cancer.
The median progression-free survival (PFS) with the combination was 3.2 months, compared with 4.2 months with nab-paclitaxel monotherapy. At 6 months, the PFS rate was 29.1% and 33.6%, respectively, and at 12 months those rates were 3.7% and 13.8%, respectively.
The median overall survival (OS) was 8.1 months in the combination arm, compared with 17.0 months in the single-agent nab-paclitaxel arm, for a hazard ratio of 1.7 (95% CI, 1.08–2.57). At 12 months, the OS rate for the two groups was 38.4% and 55.9%, respectively.
Among patients receiving the combination regimen, there were 11 responses (13.6%), and disease control was reported in 53 (65.4%). With single-agent nab-paclitaxel, these rates were 16.3% and 67.5%, respectively.
The authors reported that the treatment was generally well tolerated in both groups; 32 patients in the combination arm (40.5%) and 25 patients in the monotherapy arm (31.6%) had grade 3 or higher adverse events (AEs). The most common AEs of any grade in the combination arm included nausea (50.6%), vomiting (45.6%), and peripheral neuropathy (35.4%); in the monotherapy group, the most common AEs included peripheral neuropathy (36.7%), alopecia (26.6%), and fatigue (25.3%).
“Our study has demonstrated promising outcomes and an acceptable toxicity profile with single-agent nab-paclitaxel, without benefit from the addition of CC-486,” the authors concluded. The study also subsequently added another nonrandomized arm combining nab-paclitaxel with the anti–programmed death ligand 1 antibody durvalumab, and this group recently completed accrual.
Preliminary results of this study were previously presented at the European Society for Medical Oncology 2017 Congress in Madrid, and Martin Reck, MD, of the LungenClinic Grosshansdorf in Germany, discussed those results at the time. “The question is,” he said, “are there patients within this trial that may benefit from the combination of nab-paclitaxel and CC-486? This is a question for predictive markers; however, it is really difficult to develop predictive markers for epigenetic modifiers.” CC-486 acts as such an epigenetic modifier. Reck added that the OS data that are still to come with the combination of nab-paclitaxel and durvalumab will further illuminate the best ways to treat patients in this setting.