Data from the ABOUND 2L+ study, presented at the ESMO 2017 Congress, shows that single agent nanoparticle albumin-bound (nab) paclitaxel is promising for patients with previously treated, advanced non-small cell lung cancer (NSCLC) (Abstract LBA48).

"Immune checkpoint blockade has replaced docetaxel in patients with previously treated advanced stage NSCLC," noted study author Daniel Morgensztern, MD, Associate Professor in the Division of Medical Oncology and Director of Thoracic Oncology at the Washington University School of Medicine, St. Louis, Mo. "Nevertheless, prolonged benefit from single agent nivolumab, pembrolizumab, or atezolizumab is uncommon and most patients become eligible for additional therapy, usually with docetaxel, which has limited activity in this setting.

"Nab-paclitaxel is a cremophor-free formulation of paclitaxel that does not require pre-medication with dexamethasone and showed encouraging results as a single agent in previously treated patients with advanced NSCLC," he continued. "The combination with CC-486, an oral formulation of azacytidine, is based on preclinical synergism between epigenetic drugs and chemotherapy in NSCLC cells lines."

Daniel Morgensztern, MD. Daniel Morgensztern, MD

Patients with advanced, non-squamous NSCLC who underwent one prior line of chemotherapy were randomized 1:1 to receive nab-paclitaxel (100 mg/m² on days 8 and 15) plus CC-486 (200 mg QD on days 1-14) or nab-paclitaxel alone (100 mg/m² on days 1 and 8, both administered q3w).

After completion of the accrual, a third arm was added with the combination with durvalumab, where patients with squamous histology and prior use of immune checkpoint inhibitors were allowed, according to Morgensztern.

Grade 3 or 4 adverse events (AEs) were 59.5 percent in the combination arm compared to 54.4 percent in the nab-paclitaxel arm. The most common hematologic grade 3 or 4 AEs were neutropenia (16.5% vs. 10.1%) and anemia (1.3% vs. 7.6%). Peripheral neuropathy (grade 3 or 4) occurred in 2.5 percent of patients in the combination arm compared to 7.6 percent of patients who received nab-paclitaxel alone.

Data found that the addition of CC-486 to nab-paclitaxel did not lead to improvements in PFS (3.2 months vs. 4.2 months), OS (8.4 months vs. 12.7 months), and ORR. Researchers reported preliminary data for 79 patients in the nab-paclitaxel plus durvalumab arm, including a PFS of 4.4 months and an ORR of 20 percent. Median OS was not estimable at this time.

"The study showed that single agent nab-paclitaxel was associated with a similar median PFS compared to historical data on docetaxel," Morgensztern reported. "However, the safety profile with lower rates of neutropenia and febrile neutropenia, as well as the median OS of 12.7 months, are encouraging.

"Although the combination with CC-486 was well-tolerated, it did not provide benefit compared to single agent nab-paclitaxel," he continued. "The combination of nab-paclitaxel with durvalumab was also well-tolerated and the results are still immature for conclusions on efficacy."

Given the promising results of this study, nab-paclitaxel should be considered an effective and well-tolerated alternative to docetaxel in patients with previously treated, advanced stage NSCLC, according Morgensztern.

"Ongoing studies including the J-AXEL, which is a randomized phase III trial comparing nab-paclitaxel to docetaxel, will further define the best approaches in patients with previously treated NSCLC," he concluded.

Catlin Nalley is associate editor.