Dr. Susan M. Nedza Case Study A 52 year old gentleman was diagnosed with stage IV pancreatic cancer with liver and lung metastases. His initial therapy included FOLFIRINOX, a 5-FU based combination with irinotecan, leucovorin and oxaliplatin. Imaging studies showed disease progression after 3 months of treatment. The oncologist is now requesting bevacizumab (Avastin), and plans to add it to the current regimen. Background Pancreatic cancer is a highly lethal malignancy, with a 5 year overall survival rate of 5%. In the setting of metastatic disease, this cancer is uniformly fatal, with a median survival of approximately 6 months. Treatment has been used primarily as a palliative measure, for clinical benefit and symptom improvement. Gemcitabine combinations Gemcitabine has been the backbone of pancreatic cancer treatment since 1996, and multiple combinations have been studied since that time. Unfortunately, very few treatments have led to a significant improvement in overall survival. A recent exception has been the use of gemcitabine in combination with nab-paclitaxel (Abraxane® ). The MPACT trial, which compared this combination with single agent gemcitabine, showed an increase in overall survival with combination therapy (8.5 months vs. 6.7 months). FOLFIRINOX A randomized, phase III trial (PRODIGE) published in 2011 evaluated the combination (FOLFIRINOX) versus single agent gemcitabine in patients with metastatic pancreatic cancer and good performance status. Combination therapy demonstrated significant improvement in progression-free survival and median overall survival, but with significantly greater toxicity than gemcitabine alone. This regimen has been added to the National Comprehensive Cancer Network (NCCN) guidelines as a category 1 recommendation for first-line treatment of metastatic pancreatic cancer in patients with good functional status. Bevacizumab (Avastin®) The introduction of bevacizumab (Avastin®) has been groundbreaking in cancer treatment, demonstrating efficacy in colorectal cancer and lung cancer, among others. Side effects are considered to be generally mild, with high blood pressure and mild nosebleeds among the most common. Though rare, Avastin® has also been linked to gastrointestinal perforation, thrombosis, and fatal hemorrhage. With respect to pancreatic cancer, however, randomized phase III studies of gemcitabine in combination with Avastin® have failed to demonstrate improvements in overall survival, progression-free survival, or overall response rates. Furthermore, there was a significant increase in hypertension and proteinuria, though no toxic deaths were reported.

Discussion In our case, the patient has received a 5-FU-based regimen with disease progression. To date, there have been no published studies demonstrating the efficacy or safety of adding Avastin® to this regimen. Because of its efficacy in other tumor types and some activity demonstrated in Phase I/II trials, this drug is often requested off-label. Current consensus opinion would recommend either gemcitabine/gemcitabine combination or a 5FU-based regimen for first-line treatment. Upon progression, NCCN recommends a change to a regimen with a different backbone. In the case presented, changing to a gemcitabine-based regimen would be the recommended approach. Current evidence does not support the use of bevacizumab (Avastin®) for pancreatic cancer. In cases such as this, a pathways program can guide the ordering physician in selecting an evidence-supported approach and discourage continuation of a failing regimen. We believe that providing physicians with advanced cancer treatment decision support will translate into improved, cost-effective care. Learn more about AIM’s Integrated Oncology Solution here.

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