Michel Ducreux, MD, PhD, of the Institut Gustave Roussy in Villejuif, France, discussed the findings at the ESMO meeting. He said that TH-302 represents a “new drug and new concept, the microenvironment.” He noted, “Pancreatic cancers are frequently hypovascularized, at least the primary tumor, and there is good rationale for the use of a drug that is cytotoxic under hypoxic conditions.”

He called the trial “a well done randomized phase II trial in a well-balanced population,” but questioned the continuation of the low-dose arm and the inclusion of both advanced and metastatic patients. “We know these are different populations, and even within locally advanced disease there are two categories. This is not the way to run trials in pancreatic cancer,” he maintained.

He also had some concerns about hematologic toxicity with the higher dose, which was associated with grade 3 or 4 thrombocytopenia (63%), neutropenia (60%), and anemia (27%). “This drug is probably a little difficult to handle,” he figured.

Additional Concerns

He further questioned whether gemcitabine is the “adequate drug” to combine with TH-302. “We always use gemcitabine as the standard of care and compare the new regimen with it, but we know this not so good for metastatic disease,” he said. “In the future, the backbone of treatment in advanced and metastatic pancreatic cancer will not be gemcitabine.”

Dr. Ducreux also described other novel approaches that target the microenvironment in advanced pancreatic tumors, including nab-paclitaxel (Abraxane), which has the advantage of having a predictive biological test (SPARC level). He even questioned whether targeted therapy is appropriate for this disease. Other targeted therapies, including cetuximab (Erbitux), bevacizumab (Avastin), and to some extent erlotinib (Tarceva) have “failed to change the dismal prognosis of these tumors.”

In conclusion, he said that TH-302 has shown consistent efficacy, good response rates, a clearly positive progression-free survival benefit, a marginally positive overall survival benefit, and a favorable toxicity profile, “so there is hope here.” ■

Disclosure: Dr. Ducreux reported no potential conflicts of interest.