Τρίτη, 19 Απριλίου 2016

IMMUNOTHERAPY FOR MESOTHELIOMA

Immunotherapy with a live bacterium combined with chemotherapy demonstrated more than 90% disease control and a 59% response rate in patients with malignant pleural mesothelioma, according to the results of a phase Ib trial presented by Jahan et al April 14 (Abstract 208O_PR) at the European Lung Cancer Conference (ELCC) 2016 in Geneva, Switzerland.
“Malignant pleural mesothelioma is a cancer of the lining of the lung and is rare but difficult to treat,” said Thierry Jahan, MD, Professor of Medicine at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer. “Standard-of-care treatment with pemetrexed [Alimta] and platinum compound chemotherapy gets a 30% response rate but a modest impact on survival. So there is a clear unmet need in targeting this specific population.”
Patients with malignant pleural mesothelioma strongly express the mesothelin antigen in the tumor. CRS-207 is a live, attenuated Listeria monocytogenes bacterium that contains two gene deletions to diminish its pathogenicity and has also been engineered to express mesothelin.
“In our early studies, CRS-207 induced an antimesothelin response and cellular tumor specific immunity in patients with mesothelin-expressing tumors,” said Dr. Jahan. “We also have data suggesting that this immunotherapy works synergistically with chemotherapy, so testing the effect of this immune targeting agent with chemotherapy was a natural step.”
Study Findings
The current study examined the impact of CRS-207 combined with standard chemotherapy in patients with advanced unresectable mesothelioma who were candidates for chemotherapy. It included 38 patients who received two CRS-207 infusions 2 weeks apart; up to six cycles of pemetrexed plus cisplatin 3 weeks apart; followed by two additional CRS-207 infusions 3 weeks apart. Eligible patients received maintenance CRS-207 every 8 weeks. Patients were followed every 8 weeks until disease progression.
After a median follow up of 9.4 months (range: 0.2–28.1 months), the investigators found that 59% of patients had a partial response and 35% had stable disease, for an overall 94% disease control rate. Median progression-free survival was 8.5 months. Dr. Jahan said, “Patients receiving the combination of CRS-207 and chemotherapy had a deep response, with more than 90% disease control.”
The primary side effects associated with CRS-207 administration were temperature spike and rigors. These were related to the infusion and resolved within 24 hours. “The safety of the agent was remarkable,” said Dr. Jahan. “It really does appear to be safe, and was well tolerated in combination with pemetrexed and platinum chemotherapy. There didn’t seem to be any cumulative toxicity.”
Immunohistochemistry analysis in three patients showed marked recruitment and expansion of tumor-infiltrating leukocytes following the administration of the therapy. There was also an enhancement of infiltrating CD8-positive cells, macrophages, and natural killer cells.
Dr. Jahan said, “We saw good immune activation which confirmed the preclinical hypotheses for utilizing this agent. It appears to activate both innate and adaptive immunity and then develops a synergistic efficacy with the chemotherapy.”
He concluded, “CRS-207 is an exciting agent for patients with mesothelioma. Our preliminary results are encouraging, suggesting superior clinical activity when added to standard chemotherapy. This supports assessing the impact of CRS-207 in a randomized trial, which is currently in the planning stages and should be underway within this calendar year.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.

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