Final overall survival from a phase 3 trial of nab-paclitaxel versus dacarbazine (DTIC) in chemotherapy-naive patients with metastatic melanoma

Evan Hersh, Michele Del Vecchio, Michael Paul Brown, Richard Kefford, Carmen Loquai, Alessandro Testori, Shailender Bhatia, Ralf Gutzmer, Andrew Mark Haydon, Caroline Robert, Mingyu Li, Ileana Elias, Markus Frederic Renschler, Axel Hauschild

Research output: Contribution to journalMeeting abstract

Abstract

Background: In a phase 3 trial, nab-paclitaxel significantly improved progression-free survival (PFS) compared with DTIC (4.8 vs 2.5 months; hazard ratio [HR] 0.792; P = 0.044) in chemotherapy-naive patients with metastatic melanoma thereby meeting the primary study endpoint. A trend toward improved overall survival (OS; HR 0.831; P= 0.094) at the interim analysis (64% of patients with an event) was also shown. Here we report the final OS analysis.

Methods: 529 patients with chemotherapy-naive, stage IV melanoma (M1c, 65%; elevated lactate dehydrogenase [LDH], 28%) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomized to receive nab-paclitaxel 150 mg/m2 on days 1, 8, and 15 of a 28-day cycle (n = 264) or DTIC 1000 mg/m2 on day 1 of each 21-day cycle (n = 265). The randomization was stratified by metastatic stage, region, and baseline LDH. BRAF status was known in 67% of patients; of these, 37% had mutant and 63% had wild-type BRAF melanoma. September 20, 2013, was the clinical cutoff date for the final OS analysis.

Results: At the final OS analysis (median follow-up, ≈ 30 months for censored patients), 427 patient deaths occurred: 215 (81%) in the nab-paclitaxel vs 212 (80%) in the DTIC arm. Median OS trended in favor of nab-paclitaxel, but did not reach statistical significance vs DTIC (12.6 vs 10.5 months; HR 0.897;95% CI 0.738 - 1.089; P = 0.271. OS favored nab-paclitaxel vs DTIC across most patient subgroups, including patients aged ≥ 65 years and those with M1c stage disease, elevated LDH, and any BRAF status melanoma. The use of poststudy anticancer therapy did not differ by treatment arm, with 77% vs 73% of patients in the nab-paclitaxel arm vs DTIC arm receiving poststudy therapy. The use of a BRAF inhibitor (13% vs 10%) or ipilimumab (31% vs 32%) was also similar between treatment arms. As previously reported, the most common grade ≥ 3 adverse events with nab-paclitaxel were peripheral neuropathy (25% vs 0% with DTIC) and neutropenia (20% vs 10% with DTIC).

Conclusions: The study met the primary endpoint with a significant improvement in PFS. At final analysis, nab-paclitaxel continued to demonstrate a trend toward improved OS vs DTIC. Clinical trial information: NCT00864253.
Original languageEnglish
Pages (from-to)9045
Number of pages1
JournalJournal of Clinical Oncology
Volume32
Issue number15 Supplementary
DOIs
Publication statusPublished - 20 May 2014
Externally publishedYes
Event50th Annual Meeting of the American-Society-of-Clinical-Oncology - Chicago, United States
Duration: 30 May 20143 Jun 2014

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