“Patients with liver metastases uniformly had significantly worse median OS as compared to other sites of recurrence,” she noted, which included locoregional, peritoneum, bone, and distant sites; 23 patients had multiple sites of recurrence. They found only CA19-9 to be a significant prognostic factor; patients with lung recurrences who had a CA19-9 level greater than 185 U/mL at diagnosis had a 5-fold greater risk of death.
A global randomized phase 3 study explored the use of masitinib, a selective c-Kit inhibitor, in combination with gemcitabine compared with gemcitabine alone in 348 patients with chemotherapy-naïve pancreatic cancer.10,11
Although the combination did not significantly improve OS, Gael Deplanque, MD, of Groupe Hospitalier St. Joseph, Paris, France, and colleagues found that masitinib plus gemcitabine led to a significant survival advantage in two subpopulations: patients with pain at baseline and in those with a specific deleterious genomic biomarker.10
In patients with pain, median OS was 8.1 months in the masitinib plus gemcitabine arm compared with 5.4 months in the gemcitabine-alone arm (HR, 0.61; 95% CI: 0.42–0.88; P=0.01). OS rates at 12 and 18 months were 32.3% and 18.2%, respectively, in the masitinib plus gemcitabine arm and 17.8% and 7.8% in the gemcitabine-alone arm.10
In those with the deleterious genomic biomarker, median OS was 11 months in the masitinib plus gemcitabine arm versus 5 months in the gemcitabine-alone arm (HR, 0.29; 95% CI: 0.17–0.51; P=0.000038). At 12 and 18 months, rates of OS were 41.4% and 18.5%, respectively, in the masitinib plus gemcitabine arm compared with 11.1% and 4.2% in the gemcitabine-alone arm.10
Patients in the gemcitabine-alone arm without pain had a median OS of 15.4 months; for those without the deleterious biomarker, OS was 14.3 months. The combination of masitinib plus gemcitabine was contraindicated in these two groups, the investigators noted.10
The first randomized, placebo-controlled trial to evaluate the combination of gemcitabine with a mitogen-activated protein kinase/ERK kinase (MEK) inhibitor reported activity with the oral MEK1/2 inhibitor, trametinib, as monotherapy and in combination with gemcitabine for the treatment of patients with untreated metastatic pancreatic cancer.12[Infante Abstract],13 However, its addition did not significantly improve OS, the primary end point, noted Jeffrey R. Infante, MD, of Sarah Cannon Research Institute, Nashville, TN, and colleagues.
In the phase 2 study, median OS was 8.4 months with trametinib plus gemcitabine compared with 6.7 months for gemcitabine alone (HR, 0.98; 95% CI: 0.67–1.44; P=0.453). Patients in the combination arm had an increased incidence of skin, gastrointestinal, and hematologic toxicities.12
The 2013 Gastrointestinal Cancers Symposium is co-sponsored by the American Gastroenterological Association (AGA) Institute, the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Surgical Oncology (SSO).