Nab-Paclitaxel Extends PFS Versus Standard Chemotherapy in Patients With Metastatic Melanoma

Evan M. Hersh, MD

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A phase III trial that compared -paclitaxel (-P; Abraxane) with dacarbazine (DTIC) in patients with metastatic malignant melanoma (MMM) found that -P nearly doubled the median time to progression-free survival (PFS), suggesting that it might be a superior treatment option when compared with the standard chemotherapy regimen currently offered to patients.

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The international randomized, open-label CA033 trial enrolled chemotherapy-naïve patients with stage IV MMM who had no brain metastases. Patients were randomized to receive either 150 mg/m2 of -P on days 1, 8, and 15 every 4 weeks (n = 264) or 1000 mg/m2 of DTIC every 3 weeks (n = 265). PFS was the primary endpoint, with overall survival (OS) serving as the secondary endpoint. Other endpoints included objective response rate (ORR), disease control rate (DCR), and safety and tolerability.

The baseline characteristics of patients in both arms were well balanced. The majority of patients were male (66%), had an ECOG performance status of 0 (71%), and had M1c classified disease (65%), meaning either the melanoma had metastasized to other organs or had spread to any distant site with elevated levels of serum lactate dehydrogenase (LDH).

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In the intent-to-treat population, the study found that the median PFS among patients who received -P was 4.8 months compared with 2.5 months in the DTIC arm (HR = 0.792; 95.1% CI, 0.631-0.992; P = .044). An interim analysis showed that the median OS among the -P arm was 12.8 months compared with 10.7 months with DTIC, although those results did not achieve statistical significance (HR = 0.831; 99.9% CI, 0.578-1.196; P = .094).

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The authors reported that 73% of patients received subsequent therapies. An independent analysis found that the ORR was 15% in patients who received -P compared with 11% in the DTIC arm (P = .239) and the DCR was 39% versus 27%, respectively (P = .004).

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Phase III Results Comparing -Paclitaxel With Dacarbazine

Treatment

Median OS

Median PFS

ORR

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-paclitaxel

12.8 mo

4.8 mo

15%

Dacarbazine

10.7 mo

2.5 mo

11%

P

value

.094

.044

.239

Mo indicates months; ORR, objective response rate; OS, overall survival; PFS, progression-free survival.

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In the CA033 study, the most common grade >3 treatmentrelated adverse events that were reported in >10% of patients were neuropathy, which was reported in 25% of -P patients and 0% of DTIC patients (P < .001), with a median time to improvement of 28 days, and neutropenia, which was reported in 20% of -P patients versus 10% of DTIC patients (P = .004).

“Metastatic melanoma presents significant treatment challenges due in part to limited therapies, low survival rates at diagnosis, and no advances in chemotherapy in 37 years,” said Evan M. Hersh, MD, lead principal investigator and professor of Medicine at the University of Arizona College of Medicine and Arizona Cancer Center in Tucson, and lead author of the CA033 study, in a statement. “Despite advances with targeted treatment and immunotherapies, there is still a need for new agents including chemotherapy treatments for patients with metastatic melanoma.”

The results of the trial were presented at the Society for Melanoma Research 2012 Congress in Hollywood, California.

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-paclitaxel is a nanoparticle-sized anticancer compound delivered as an injection that uses human albumin, a water-soluble protein, as a shell to house the active drug. The shell binds to the tumor, and the therapeutic agent is released in a targeted dose, initiating apoptosis. The agent is already approved by the FDA to treat metastatic breast cancer after failure on combination chemotherapy and untreated locally advanced non—small cell lung cancer in patients who are not candidates for radiation or surgery.

Pigment Cell Melanoma Res

Hersh E, Del Vecchio M, Brown M, et al. Phase 3, randomized, open-label, multicenter trial of nab-paclitaxel (nab-P) versus dacarbazine (DTIC) in previously untreated patients with metastatic malignant melanoma (MMM). . 2012;25(6): 863.