The initial results of a randomized phase III clinical trial of nanoparticle albumin bound (nab)-paclitaxel (Abraxane) used with carboplatin indicates that this combination results in superior objective response rates in advanced non-small cell lung cancer (NSCLC) compared with paclitaxel/carboplatin. The trial-a multicenter study that randomly assigned more than 1,000 patients from Russia, the Ukraine, Japan, North America, and Australia to one of the two combinations-was designed in conjunction with the FDA to determine whether nab-paclitaxel should receive an indication in NSCLC.¹

Survival Analysis Forthcoming

The positive results concerning objective response rates-if bolstered by upcoming overall and progression-free survival data-may help make the case for nab-paclitaxel to receive an indication in NSCLC, said Alan Sandler, MD, Professor of Medicine and Chief of the Hematology and Medical Oncology Division at the Oregon Health & Science University's Knight Cancer Institute. Dr. Sandler presented the study results at the Best of ASCO Meeting in San Francisco.¹

"Since this is an agent that is a derivative of another approved agent (paclitaxel), all the study needs to show is similarities in outcome. In this case, the study was designed to show improvements in response rate," Dr. Sandler said. Objective response as determined by an independent radiologic review committee according to RECIST criteria was the primary endpoint of the study. The investigators also assessed objective response. Secondary endpoints included progression-free survival (PFS), overall survival, disease control rate, and safety and toxicities. The PFS analysis will be presented later this year, said lead researcher Mark A. Socinski, MD, of the University of North Carolina at Chapel Hill.

In the study, 1,050 patients with stage IIIB or IV NSCLC with a performance status of 0 or 1 were randomly assigned to receive carboplatin at an AUC of 6 every 3 weeks and either nab-paclitaxel at 100 mg/m² weekly with no premedication or paclitaxel at 200 mg/m² every 3 weeks with dexamethasone and antihistamine premedication. Patients received a median of six cycles of therapy.

Key Data

Results indicated that the objective response rate for nab-paclitaxel/carboplatin was 33% vs 25% for paclitaxel/carboplatin, as determined by independent radiologic review. As judged by investigator assessment, the objective response rate for patients treated with nab-paclitaxel was again superior to those who received paclitaxel (37% vs 30%). The nab-paclitaxel/carboplatin combination was particularly beneficial for patients with squamous cell carcinoma, with an objective response rate of 41% vs 24% in the paclitaxel/carboplatin arm, as assessed by radiologic review. Investigator assessment indicated that the objective response rate for patients with squamous cell carcinoma on nab-paclitaxel/carboplatin was 37% vs 29% for paclitaxel/carboplatin.

Grade 3 or 4 sensory neuropathy, myalgia, and neutropenia occurred in significantly more patients on paclitaxel than nab-paclitaxel  (10% vs 3%, 2% vs < 1%, and 56% vs 45%, respectively). In contrast, grade 3 or 4 thrombocytopenia and anemia were significantly more likely in patients who received nab-paclitaxel than among those on paclitaxel (17% vs 8% and 27% vs ~6%, respectively).

In addition to showing superior efficacy, the nab-paclitaxel combination had an improved safety profile compared to the paclitaxel/carboplatin doublet, Dr. Socinski said at the Annual Meeting. "We have to wait for additional data with respect to progression-free survival, but my guess is that this agent will obtain an indication in non-small cell lung cancer," Dr. Sandler commented. ■

Reference

1. Socinski MA, Bondarenko IN, Karaseva NA, et al. Results of a randomized, phase III trial of nab-paclitaxel and carboplatin compared with cremophor-based paclitaxel and carboplatin as first-line therapy in advanced non-small-cell lung cancer. Best of ASCO Annual Meeting San Francisco. Abstract LBA7511. Presented July 17, 2010, by Alan Sandler, MD.