AMSTERDAM—Oral immunotherapy with talactoferrin alfa appears to decrease the risk of dying in patients treated for severe sepsis resulting from a urinary tract infection (UTI) or other causes, researchers announced at the 14th World Conference on Lung Cancer.
“Pre-clinically, there were signs that talactoferrin could help regulate immune response in the infection setting,” said Jeffrey Crawford, MD, Chief of the Division of Medical Oncology at Duke University Medical Center in Durham, N.C. “Clinically…our small but nonetheless almost 200-patient study produced very encouraging results for infections at almost all sites, with particularly impressive results in the subset of patients with urinary tract infections.”
Talactoferrin, an investigational agent, has also demonstrated activity in non-small cell lung cancer as monotherapy in the second- and third-line setting and when added to a first- line chemotherapy doublet.
Dr. Crawford presented findings from a phase 2 study in which 190 patients were randomized to talactoferrin 1.5 g or placebo enterally every eight hours for a maximum of 28 days in addition to standard best supportive care including (at the doctor’s discretion) activated drotrecogin alfa.
Severe sepsis is a significant medical problem affecting as many as 750,000 patients in the United States each year, and mortality can be as high as 50%, Dr. Crawford said. Supportive care remains the cornerstone of therapy.
Activated protein C is the only drug treatment specifically approved for treatment, however “the effect is somewhat marginal, and a recent Cochrane analysis was not able to show an improved survival with this treatment.”
All patients in the present study had developed severe sepsis within 24 hours, which was defined as known or suspected infection with at least two of four systemic inflammatory response criteria and at least one acute organ dysfunction due to sepsis that could be cardiovascular, respiratory, renal, hematologic, or metabolic.
The analysis showed a 28-day mortality rate of 26.9% in the intent-to-treat population of severely septic patients who received placebo plus best supportive care versus 14.4% in patients who received talactoferrin plus best supportive care, which translates into a 46.5% relative reduction in 28-day mortality with talactoferrin. “The mortality reduction with talactoferrin treatment far exceeds what’s been seen with any other intervention,” Dr. Crawford observed.
UTIs accounted for 23% of infections in the placebo arm and 21% of infections in the talactoferrin arm and were the most common infection after lung infections, which occurred in 52% of the placebo arm and 46% of the talactoferrin arm. “These rates of infection are typical of what we see in the community,” Dr. Crawford observed.
In the subgroup of patients with urinary tract infection, the 28-day mortality rate was 29% in placebo-treated patients and 5% in talactoferrin-treated patients.
The analysis showed that the mortality rate was consistently lower in the talactoferrin arm across all infection sites with the exception of intra-abdominal infections.
Talactoferrin well tolerated.
Dr. Crawford said that while the present study was not conducted in a cancer population but rather in patients who were in an intensive care unit because of complications of severe sepsis, the findings have potential relevance for cancer patients. “Cancer patients are at increased risk of sepsis because their immune systems may be depressed by the treatments they receive,” he said. “Frequent hospitalization, surgeries and weakness due to illness may also raise the risk of sepsis in cancer patients.”
Finally, he emphasized that the data are preliminary. “This was a randomized phase 2 study that was not powered to prove definitively that this drug is effective in reducing mortality from sepsis but rather it was set up to determine if there is clinical evidence to show that that might be the case,” he said. “And that’s the basis for a phase 2/3 study with talactoferrin in patients with sepsis that is currently underway.”