FDA Approves Nab-Paclitaxel for Advanced Lung Cancer

Mark A. Socinski, MD

The FDA has approved nab-paclitaxel (Abraxane) plus carboplatin for patients with untreated locally advanced or metastatic non-small cell lung cancer (NSCLC) who are not candidates for surgery or radiation.

The approval was based on results from the phase III CA031 trial, which showed that weekly nab-paclitaxel, a nanoparticle albumin-bound (nab) formulation of paclitaxel, combined with carboplatin significantly improved overall response rate (ORR), when compared with solvent-based (sb) paclitaxel plus carboplatin.

“The FDA approval of Abraxane is exciting for healthcare professionals because it offers an important new treatment option for all types of non-small cell lung cancer patients, in an area that has seen few treatment advancements in recent years," said Mark A. Socinski, MD, director of the Lung Cancer Section in the Division of Hematology/Oncology at the University of Pittsburgh and the lead investigator of the CA031 trial.

The phase III CA031 trial enrolled 1052 patients who had not received prior treatment for stage IIIB to IV NSCLC. On the trial, patients were randomized 1:1 to receive carboplatin every 3 weeks at AUC6 mg/mL/min plus 100 mg/m² of weekly nab-paclitaxel or 200 mg/m² of sb-paclitaxel every 3 weeks.

The nab-paclitaxel arm demonstrated a significantly higher ORR than sb-paclitaxel (33% versus 25%; response rate ratio, 1.313; 95% CI, 1.082-1.593; P = .005). Additionally, the trial found that patients with squamous histology who received nab-paclitaxel experienced more than a doubling in response when compared with sb-paclitaxel (41% versus 24%; response rate ratio, 1.680; 95% CI, 1.271-2.221; P < .001).

Secondary survival endpoints were assessed on the trial but did not yield statistically significant results. The progression-free survival for nab-paclitaxel was 6.3 months compared with 5.8 months for those receiving sb-paclitaxel (HR, 0.902; 95% CI, 0.767 to 1.060; P = .214). The median overall survival was 12.1 months for nab-paclitaxel and 11.2 months for sb-paclitaxel (HR, 0.922; 95% CI, 0.797 to 1.066; P = .271).

In a safety analysis presented at the 2012 ASCO Annual Meeting, investigators examined the patient-reported neuropathy and taxane-associated symptoms from the CA031 trial. This analysis examined 1031 patients at baseline and 987 during a follow-up.

The analysis found that nab-paclitaxel was associated with a significant reduction in peripheral neuropathy (P < .001), patient-reported neuropathy (P < .001), and hearing loss (P = .002) compared with sb-paclitaxel. Additionally, the physician-assessed rates of all-grade neuropathy were 47% for those treated with nab-paclitaxel compared with 63% for those receiving paclitaxel (P < .001).

This marks the second indication for nab-paclitaxel, which is manufactured by Celgene Corporation. The agent was first approved in 2005 for the treatment of metastatic breast cancer after failure of combination chemotherapy.

Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non—small-cell lung cancer: final results of a phase III trial [published online ahead of print April 30, 2012]. J Clin Oncol. doi: 10.1200/JCO.2011.39.5848.

Hirsh V, Okamoto I, Hon JK, et al. Weekly nab-paclitaxel in combination with carboplatin as first-line therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC): Analysis of patient-reported neuropathy and taxane-associated symptoms. J Clin Oncol. 2012;30(suppl; abstr TPS7618).