Nab-Paclitaxel as Possible Option for Relapsed NSCLC

Patients with previously treated advanced non-small cell lung cancer had similar overall survival (OS) with docetaxel and nab-paclitaxel (Abraxane), but the latter improved progression-free survival (PFS) and was better tolerated, a randomized trial showed.

Median OS improved from 13.6 months with docetaxel to 16.2 months with nab-paclitaxel. The difference did not achieve statistical significance but met the trial’s primary objective of noninferiority. The protein-bound paclitaxel formulation offered a slight PFS advantage and led to a significantly higher objective response rate (ORR).

Grade 3/4 hematologic toxicity and febrile neutropenia occurred substantially more often with docetaxel, whereas nab-paclitaxel caused more peripheral sensory neuropathy, reported Atsushi Nakamura, MD, of Sendai Kousei Hospital in Miyagi, Japan, during the virtual World Conference on Lung Cancer.

“The primary objective of the study was met — confirmation of the noninferiority of nab-paclitaxel compared with docetaxel in terms of overall survival, and superiority (for nab-paclitaxel) was apparent with regard to progression-free survival,” Nakamura said in conclusion. “Nab-paclitaxel should be considered a standard option for previously treated patients with advanced non-small cell lung cancer.”

Single-agent docetaxel has a long history as the second-line standard for advanced NSCLC, and the trial results are unlikely to change that, according to invited discussant Sai-Hong Ignatius Ou, MD, PhD, of the University of California Irvine. The drug has stood the test of time since demonstrating superiority in the placebo-controlled TAX317 trial and in the TAX320 trial comparing docetaxel, vinorelbine, and ifosfamide more than 20 years ago.

Second-line docetaxel has continued to produce results comparable to newer agents, including biologics and targeted therapies, Ou continued. The drug continued to prevail in multiple studies of add-on therapy, with the exception of the REVEL trial that evaluated docetaxel with or without ramucirumab (Cyramza).

“[REVEL] was a positive study even though the overall improvement (in OS) was about 1.4 months,” said Ou. “This is a regimen that I use, but it doesn’t look like it’s widely adopted globally, most likely because of cost. Most of the studies, with the exception of REVEL, showed that single-agent docetaxel remains the standard of care.”

More recently, immuno-oncology trials have demonstrated superiority in relapsed NSCLC with nivolumab (Opdivo), pembrolizumab (Keytruda), and atezolizumab (Tecentriq) versus docetaxel. Only the JAVELIN Lung 200 trial with avelumab (Bavencio) failed to outperform single-agent docetaxel, said Ou.

“Docetaxel at 60 mg/m² is actually pretty efficacious,” said Ou. “[Nakamura] concluded that nab-paclitaxel is a potential regimen. However, most of the drugs that have been studied (in second line) have been moved to first-line treatment, moved up to combination. At this point, it seems like docetaxel remains the standard.”

Interest in nab-paclitaxel for NSCLC has support from various studies suggesting potential advantages with the protein-bound formulation, including pharmacokinetics, antitumor activity, and toxicity, said Nakamura. In a phase II trial of previously treated NSCLC, treatment with single-agent nab-paclitaxel resulted in an ORR of 32% and median PFS of 5 months. The results provided a rationale for continued evaluation in the phase III J-AXEL trial.

Investigators at centers throughout Japan enrolled patients with previously treated stage IIIb/IV or recurrent NSCLC and randomized them to docetaxel or nab-paclitaxel. The primary objective was to demonstrate OS noninferiority for nab-paclitaxel versus docetaxel within a hazard ratio (HR) range of 1.33 to 1.25 with hierarchical testing.

Data analysis comprised 503 patients, most of whom had received one prior line of chemotherapy for advanced NSCLC. About 16% of the patients had received an immune checkpoint inhibitor.

The 2.6-month absolute difference in median OS in favor of nab-paclitaxel translated into an HR of 0.85, which met criteria for noninferiority (95% CI 0.68-1.07). Median PFS was 4.2 months with nab-paclitaxel and 3.4 months with docetaxel (HR 0.76, 95% CI 0.63-0.92, P=0.0042). ORR also favored nab-paclitaxel in the overall analysis (29.9% vs 15.4%, P=0.0002), in the subgroup with squamous histology (30.4% vs 10.4%, P=0.0207), and in patients with nonsquamous NSCLC (29.7% vs 16.7%, P=0.0042).

Docetaxel was associated with significantly more grade 3/4 leukopenia (65.9% vs 25.7%, P<0.0001), neutropenia (83.1% vs 39.6%, P<0.0001), febrile neutropenia (22.1% vs 2.0%, P<0.0001), and fatigue (55.2% vs 38.8%, P=0.0029). Grade 3/4 peripheral sensory neuropathy occurred significantly more often with nab-paclitaxel (55.5% vs 20.1%, P<0.0001).