ESMO 2017 Press Release: Combination Immunotherapy in Second/third Line Extends Mesothelioma Survival to 15 Months

Excerpt:

“Combination immunotherapy as second or third line treatment extends overall survival to at least 15 months in patients with pleural malignant mesothelioma, according to late-breaking results from the MAPS2 trial presented today at the ESMO 2017 Congress in Madrid.

“Malignant pleural mesothelioma (MPM) is a rare disease usually caused by occupational exposure to asbestos. First line therapy is pemetrexed and platinum chemotherapy, with or without bevacizumab. There is no approved second line treatment and drugs that have been tested in this setting had low efficacy, with a disease control rate under 30%. Phase II studies have shown promising activity of checkpoint inhibitors as second line treatment.”

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Nintedanib Chemo Combo Shows Benefit in Frontline Mesothelioma

Excerpt:

“Treatment with nintedanib plus pemetrexed and cisplatin improved progression-free survival (PFS) in the frontline setting by 3.7 months for chemotherapy-naive patients with malignant pleural mesothelioma (MPM), according to data reported at the 2017 ASCO Annual Meeting.

“In the phase II trial, known as LUME-Meso, the median PFS was 9.4 months with the nintedanib combination versus 5.7 months with pemetrexed and cisplatin alone (HR, 0.54; 95% CI, 0.33-0.87; P = .010). The median overall survival (OS) was 18.3 months with nintedanib versus 14.2 months with chemotherapy alone; however, this finding was not statistically significant (HR, 0.77; 95% CI, 0.46-1.29; P = .319).”

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Immunotherapy Yields ‘Dramatic’ Response Rates in Relapsed Mesothelioma

Excerpt:

“Immunotherapy may represent an effective new treatment approach for relapsed mesothelioma patients, according to a new study.

“Anti–programmed death-1 (PD-1) immunotherapy may have activity as second- or third-line therapy in malignant pleural mesothelioma (MPM), an aggressive, rare cancer associated with asbestos exposure that has no curative treatment. All MPM patients relapse despite initial chemotherapy, and median overall survival (OS) is 9 months at most, said lead author Arnaud Scherpereel, MD, PhD, head of the pulmonary and thoracic oncology department at the University Hospital (CHU) of Lille in Lille, France, at a press briefing at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract LBA8507).”

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Pembrolizumab Shows Promise in Treatment of Mesothelioma

Excerpt:

“Pembrolizumab, an antibody drug already used to treat other forms of cancer, can be effective in the treatment of the most common form of mesothelioma, according to a new study led by investigators from the Perelman School of Medicine at the University of Pennsylvania. The study, published this month in The Lancet Oncology, is the first to show a positive impact from checkpoint inhibitor immunotherapy drugs on this disease.

“Malignant pleural mesothelioma is a rare and aggressive cancer that represents about 90 percent of all malignant mesothelioma cases. It’s primarily caused by the inhalation of asbestos, a fiber commonly found in some forms of insulation, vinyl floor tiles, and other material. Tumors form in the pleura, a thin membrane of cells that line the lungs and chest wall. Most survive less than a year. This poor prognosis is partially due to the fact that most patients are not diagnosed until they are already at a late stage of the disease. The standard first-line therapy treatment involves chemotherapy, and currently there is no approved second-line therapy.”

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Immunotherapy Looks ‘Promising’ in Malignant Mesothelioma

Excerpt:

“Immunotherapy is now offering hope even in one of the most aggressive cancers of all, malignant pleural mesothelioma.

“Malignant mesothelioma is usually diagnosed at a late stage and is essentially incurable. The median overall survival is approximately 12 months with first-line chemotherapy, and median survival with second-line therapy, which has not yet been adequately defined, is typically less than 10 months.

“Early clinical results with the programmed cell death (PD) inhibitors nivolumab (Opdivo, Bristol-Myers Squibb) and pembrolizumab (Keytruda, Merck & Co) show response, yielding survival rates that appear to be improvements on what has been seen historically with chemotherapy.”

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Avelumab Promising in Unresectable Mesothelioma

Excerpt:

“The novel anti-PD-L1 agent avelumab showed some promising clinical activity and was generally well tolerated in a phase I trial of patients with unresectable, previously treated mesothelioma. Results of the trial were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago.

“ ‘Approximately 3,000 new cases of malignant mesothelioma are diagnosed each year in the United States,’ said Raffit Hassan, MD, of the National Cancer Institute in Bethesda, Maryland, who presented the study. The current standard treatment of pemetrexed and cisplatin yields a median overall survival of 12.1 months, and there is no US Food and Drug Administration (FDA)-approved therapy for patients progressing after first-line chemotherapy.

“Avelumab is a fully human anti-PD-L1 IgG1 antibody; it is under investigation in multiple malignancies. PD-L1 is expressed on the surface of mesothelioma cells, providing a rationale for avelumab’s use in this malignancy. In the new JAVELIN study, more than 1,600 patients have been treated with the drug across a variety of malignancies; in this analysis, 53 patients with unresectable pleural or peritoneal mesothelioma were included. All patients had progressed after a platinum/pemetrexed-containing regimen; they were unselected for PD-L1 expression.”

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Expert Discusses Promise of CRS-207 Vaccine in Mesothelioma

Excerpt:

“The investigational cancer vaccine CRS-207 may improve response and survival when given with chemotherapy in patients with malignant pleural mesothelioma (MPM) according to results of a phase Ib trial.

“CRS-207, a live-attenuated, double-deleted Listeria monocytogene engineered to express the tumor-associated antigen mesothelin, was administered with chemotherapy to 38 patients with MPM. Of 34 evaluable patients, 59% (n = 20) had partial response posttreatment and 35% (n = 12) had stable disease, for an overall disease-control rate 94%. Median progression-free survival was 8.5 months and median overall survival had not been reached.

“Immunohistochemistry data from 3 patients revealed an increase in tumor-infiltrating lymphocytes (TILs) post–CRS-207. Treatment-associated changes in circulating immune cells and biomarkers were also observed.”

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ELCC 2016 Press Release: Immunotherapy With Live Bacterium Improves Response Rate in Malignant Pleural Mesothelioma

Excerpt:

“Immunotherapy with a live bacterium combined with chemotherapy demonstrated more than 90% disease control and 59% response rate in patients with malignant pleural mesothelioma (MPM), according to the results of a phase Ib trial presented today 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 Prof Thierry Jahan, professor of medicine at the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco, US. ‘Standard of care treatment with pemetrexed 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 MPM strongly express the mesothelin antigen in the tumour. 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.”

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FDA Grants Orphan Drug Designation to WT1 Cancer Vaccine for Malignant Pleural Mesothelioma

“The FDA granted orphan drug designation to the WT1 cancer vaccine for the treatment of malignant pleural mesothelioma.

“The FDA based the designation on results from a randomized, double blind, placebo-controlled phase 2 trial of the WT1 vaccine (SLS-001, SELLAS Life Sciences) in 40 patients with malignant pleural mesothelioma treated at Memorial Sloan Kettering Cancer Center and The University of Texas MD Anderson Cancer Center.

“Results showed patients assigned the vaccine experienced longer median OS (21.4 months vs. 16.6 months) and median PFS (11.4 months vs. 5.7 months) than those assigned placebo. The vaccine also demonstrated a favorable safety profile, according to researchers.

“A phase 2b/3 trial in malignant pleural mesothelioma is expected to begin by the third quarter of this year.”