FDA approves Abraxane for metastatic pancreatic cancer

Issue: October 10, 2013

The FDA today expanded the approved indications of paclitaxel protein-bound particles for injectable suspension, also known as nab-paclitaxel, to include treatment of late-stage pancreatic cancer.

Perspective from Andrew H. Ko, MD

Nab-paclitaxel (Abraxane, Celgene), a chemotherapy agent shown to slow tumor growth, is indicated for use in combination with gemcitabine (Gemzar, Eli Lilly) for patients whose pancreatic cancer has metastasized.

Richard Pazdur

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

The FDA based its approval of nab-paclitaxel on results of a trial that included 861 patients. Researchers randomly assigned patients to receive nab-paclitaxel plus gemcitabine, or gemcitabine alone.

OS served as the primary endpoint. Secondary endpoints were PFS and overall response rate as confirmed by independent review.

The combination regimen was associated with longer median OS (8.5 months vs. 6.7 months; HR=0.72; 95% CI, 0.617-0.835) and median PFS (5.5 months vs. 3.7 months; HR=0.69; 95% CI, 0.581-0.821). The overall response rate was 23% among patients assigned to nab-paclitaxel plus gemcitabine compared with 7% among patients assigned to gemcitabine alone.

Common adverse events experienced by patients treated with the combination regimen included neutropenia, thrombocytopenia, fatigue, peripheral neuropathy, nausea, hair loss, fever, vomiting, rash and dehydration, according to the FDA.

The most frequent serious side effects were fever, dehydration, pneumonia and vomiting. Sepsis and pneumonitis also were observed.

The FDA approved nab-paclitaxel for pancreatic cancer under its priority review program. The drug also is indicated for treatment of breast cancer and non–small cell lung cancer.

Perspective

Andrew H. Ko, MD

The recent FDA approval of Abraxane for metastatic pancreatic cancer, based on positive results from the international, phase 3 MPACT trial, represents an important clinical development, as we now have an additional therapeutic option available for patients in the first-line setting for this disease. Inevitable comparisons will be made between gemcitabine/ Abraxane and another combination chemotherapy regimen, FOLFIRINOX (5-FU, leucovorin, irinotecan and oxaliplatin), that has also demonstrated superior efficacy to gemcitabine monotherapy in a phase 3 trial. However, unless and until these regimens are compared directly head-to-head in a prospective study, we must refrain from our natural tendency to make cross-study comparisons, and for now, we should base treatment decisions on an individualized, patient-by-patient basis. Age, co-morbid conditions and performance status all represent key factors that weigh into this therapeutic decision-making process.

One key — and perhaps underappreciated — observation from the Abraxane trial was that patients with a marginal performance status (PS) appeared to benefit as much or more from combination treatment as did those with a better PS. Data regarding the predictive utility of SPARC (secreted protein acidic and rich in cysteine) expression in tumors should be forthcoming soon and are eagerly anticipated, as this biomarker may further help identify a subset of patients who respond particularly well to Abraxane-based therapy. The FDA’s approval of Abraxane also opens the door to a number of other important clinical questions — for example, the role of this drug in the locally advanced, neoadjuvant, adjuvant and second-line (eg, post-FOLFIRINOX) settings. These are areas that will require, and currently represent the subject of, further clinical investigation.

Andrew H. Ko, MD

HemOnc Today Editorial Board member

Disclosures: Ko reports no relevant financial disclosures.