Nab-Paclitaxel Shows Benefit in Advanced Melanoma

Treatment with nab­-paclitaxel resulted in significantly improved progression-free survival and a greater disease control rate in chemotherapy-naive patients with metastatic melanoma compared with dacarbazine, according to the results of a study published recently in Annals of Oncology.

Treatment with “nab-paclitaxel demonstrated clinically meaningful superiority compared with dacarbazine,” wrote Evan M. Hersh, MD, of the University of Arizona Cancer Center, and colleagues, “with a near doubling of median progression-free survival and a 44% improvement in disease control rate (includes patients with stable disease for ≥ 16 weeks) in chemotherapy-naive patients with metastatic melanoma.”

Based on these results, they concluded that “nab-paclitaxel can be considered in the treatment armamentarium for chemotherapy-naive patients with metastatic melanoma.”

According to the study, the use of taxanes in metastatic melanoma has had limited success; however, nab-paclitaxel-paclitaxel formulated as albumin-bound nanoparticles-has shown some efficacy in chemotherapy-naive patients.

This phase III trial randomly assigned 529 chemotherapy-naive patients with stage IV melanoma to nab-paclitaxel (n = 264) on days 1, 8, and 15, every 4 weeks, or dacarbazine (n = 265) every 3 weeks.

In the final analysis, 58% of patients assigned nab-paclitaxel and 64% assigned dacarbazine progressed or died. There was a greater than 2-month improvement in progression-free survival among patients assigned to nab-paclitaxel compared with dacarbazine (4.8 vs 2.5 months; hazard ratio [HR], 0.792 [95% confidence interval (CI), 0.631–0.992]; P=.004).

“The robustness of the progression-free survival analysis was supported with various sensitivity analyses related to off-schedule response assessments or missed study visits,” the researchers noted.

No significant difference in overall survival was seen between the two groups (12.6 vs 10.5 months; P = .271).

“Although a significant difference in progression-free survival was observed with nab-paclitaxel vs dacarbazine, a significant treatment effect of nab-paclitaxel on overall survival may have been limited by the equivalent and high rate (75%) of use of post-study therapy, including newer agents, such as BRAF inhibitors and ipilimumab, by patients in both treatment arms,” Hersh and colleagues wrote.

There was no significant difference in the overall response rate seen in patients assigned nab-paclitaxel (15%) compared with dacarbazine (11%). However, patients treated with nab-paclitaxel had significant improvements in disease control rate (P = .004) and best overall response rate (P = .002) compared with dacarbazine.

Subgroup analyses also found that nab-paclitaxel resulted in improvements in progression-free survival regardless of BRAF mutation status. In addition, nab-paclitaxel treatment resulted in greater delays in progression compared with dacarbazine among those patients with the most advanced melanoma (HR, 0.734 [95% CI, 0.558–0.965]; P = .028).

According to the study, nab-paclitaxel is currently recommended by the National Comprehensive Cancer Network (NCCN) as single-agent treatment for advanced or metastatic melanoma.

“Results of ongoing trials of nab-paclitaxel in combination with targeted therapies or novel immunotherapies may help expand this recommendation in the future, as nab-paclitaxel may provide a good backbone regimen to build upon given its safety profile,” the researchers wrote.