MPACT demonstrated a median overall survival (OS) of 8.5 months in the nab-paclitaxel plus gemcitabine arm compared with 6.7 months in the gemcitabine-alone arm (HR, 0.72; 95% CI: 0.617–0.835; P=0.000015). One-year OS rates were 35% for the combination arm and 22% in the gemcitabine-alone arm (P=0.0002); 2-year OS rates were 9% and 4% (P=0.02), respectively.3,4
“The OS benefit associated with the two-drug combination persisted across all prespecified patient subgroups. Of particular note is that, in general, the poorer the prognostic factor, the more favorable the hazard ratios for the combination,” Dr. Von Hoff said.5
Neutropenia (38% in the nab-paclitaxel plus gemcitabine arm vs. 27% in the gemcitabine arm), fatigue (17% vs. 7%), and neuropathy (17% vs. 1%) were the most common grade 3 or higher adverse events. Grade 3 or higher neuropathy improved to grade 1 or lower in 29 days. Febrile neutropenia was reported in 3% of patients in the combination arm compared with 1% in the gemcitabine arm.3
Earlier Detection, Customized Treatment?
Although surgery, radiation therapy, and chemotherapy may prolong survival or offer relief from symptoms, fewer than 20% of patients with pancreatic cancer are surgical candidates and 5-year survival is only 22% for those diagnosed with local disease.2 One reason patients have such a poor prognosis is they may have few early symptoms, and there are no widely used methods for early detection.2
For that reason, investigators are working to determine if biomarkers can be used to detect pancreatic cancer earlier or to identify candidates for surgery, and whether chemotherapy can be fine-tuned based on molecular response, a strategy towards personalized medicine already successful in other tumor types, such as lung cancer.
The first study to find circulating tumor cells (CTCs) in patients with localized pancreatic ductal adenocarcinoma “may be associated with findings of unexpected metastatic disease at surgery,”6 noted Rachel D. Aufforth, MD, of the University of North Carolina School of Medicine, Division of Surgical Oncology and Endocrine Surgery, Chapel Hill, NC.
Calling these results “surprising,” she noted “further follow-up will be needed to determine if the presence of CTCs in these patients is a harbinger of shorter progression-free survival and overall survival after curative operations.” Dr. Aufforth credits the development of newer microfluidic platforms with the ability to detect “substantially greater numbers of CTCs,” increasingly recognized as important biomarkers of disease burden.6
Commenting on the study, William M. Grady, MD, Member of the 2013 Gastrointestinal Cancers Symposium News Planning Team and American Gastroenterological Association (AGA) Institute Representative, said, “Aufforth and colleagues have developed a novel CTC detection method that substantially increases the sensitivity of the assay and appears to be useful for identifying patients with pancreatic cancer with advanced disease.
“If further studies confirm these results, this CTC biomarker assay could be used to accurately identify those patients with pancreatic cancer likely to benefit from surgical resection of the cancer, sparing those who will not benefit from surgery the morbidity associated with the operation.”