FDA Approves Nab-Paclitaxel for Advanced Pancreatic Cancer

The FDA has approved nab-paclitaxel (Abraxane) plus gemcitabine as a first-line treatment for patients with metastatic adenocarcinoma of the pancreas, an area of high unmet need with few effective treatments.

The approval was based on results from the MPACT trial, which showed that weekly nab-paclitaxel, a nanoparticle albumin-bound (nab) formulation of paclitaxel, combined with gemcitabine significantly improved both overall survival (OS) and progression-free survival (PFS), when compared with gemcitabine alone.

“For more than 15 years, treatment with gemcitabine has been the standard of care in this disease,” said Jean-Pierre Bizzari, MD, the executive vice president of Hematology and Oncology for Celgene Corporation, the company that develops the drug. “The addition of Abraxane to gemcitabine demonstrated meaningful improvements across key efficacy outcomes, including overall survival, with a well-characterized safety profile.”

The phase III MPACT trial enrolled 861 patients who had not received prior chemotherapy for metastatic pancreatic cancer with adenocarcinoma histology, which accounts for 95% of all pancreatic cancers. In the trial, patients were randomized in a 1:1 ratio to receive weekly intravenous nab-paclitaxel at 125 mg/m² plus 1000 mg/m² of gemcitabine for 3 weeks followed by 1 week of rest (n=431) or 1000 mg/m² of weekly gemcitabine for 7 weeks with 1 week of rest followed by the same schedule as the investigational arm (n=430). The primary endpoint of the trial was OS.¹

The nab-paclitaxel arm demonstrated a significantly higher OS than gemcitabine monotherapy (8.5 months versus 6.7 months; hazard ratio [HR] = 0.72; P < .0001). Additionally, the trial found a PFS advantage favoring the nab-paclitaxel combination of 5.5 months compared to 3.7 months (HR = 0.69; P < .0001). The combination also demonstrated a superior overall response rate of 23% compared with 7% for gemcitabine alone (P < 0.0001).

Additionally, for patients who went on to receive subsequent second-line therapies (38% in the nab-paclitaxel arm, 42% in the control), the median OS was 9.4 months compared with 6.8 months, for the investigational and control arms, respectively (HR = 0.68; P = .00072).

“Historically, patients with pancreatic cancer have not experienced benefit with many of the drugs so useful in other malignancies. This is beginning to change,” said Margaret A. Tempero, MD, the director and a professor of medicine at the University of California, San Francisco Pancreas Center, in a statement. “The combination of Abraxane and gemcitabine represents an important new therapeutic option for patients with pancreatic cancer. It also provides a foundation for future clinical research.”

The baseline characteristics of patients were well-balanced between the two arms. The median age was 63 years old and 43% of patients had lesions in the head of the pancreas. Additionally, 52% of patients had a much higher than normal CA19-9 marker level, indicating a worse prognosis. However, patients with poor prognostic factors had more favorable outcomes with the combination than the monotherapy.

In general, according to a subanalysis presented at the 2013 ASCO Annual Meeting, liver metastases and a Karnofsky performance status (KPS) less than 80 predicted the greatest advantage for the combination over the single agent. For patients with a KPS of 70 to 80 compared with those with 90 to 100 the HR was 1.60 (P < 0.0001) in favor of the nab-paclitaxel arm. Additionally, for patients with liver metastases compared with those without, the HR was 1.81 (P < 0.0001), suggesting several factors to predict higher levels of response to the combination.²

Richard Pazdur, MD

The most common adverse reactions with the nab-paclitaxel combination were neutropenia, fatigue, peripheral neuropathy, and nausea. However, there was no increase in life-threatening toxicity by adding nab-paclitaxel.

“Patients with pancreatic cancer are often diagnosed after the cancer has advanced and cannot be surgically removed,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “In these situations, and in situations when the cancer has progressed following surgery, options like Abraxane can help prolong a patient’s life.”

This marks the third indication for nab-paclitaxel, which was first approved in 2005 for the treatment of metastatic breast cancer after failure of combination chemotherapy. In October 2012 the agent also received approval to treat patients with untreated locally advanced or metastatic non-small cell lung cancer (NSCLC) who are not candidates for surgery or radiation.

1. Von Hoff DD, Ervin TJ, Arena FP, et al. Randomized phase III study of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic adenocarcinoma of the pancrease (MPACT). Presented at the 10th Annual Gastrointestinal Cancers Symposium; January 24-26, 2013; San Francisco, CA. Abstract LBA 148.
2. Moore MJ, Von Hoff DD, Ervin TJ, et al. Prognostic factors (PFs) of survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel (nab-P) plus gemcitabine (G) versus G alone in patients (pts) with metastatic prostate cancer. J Clin Oncol. 31, 2013 (suppl; abstr 4059).