Vaccine and Chemotherapy Combo Shows Promise for Mesothelioma

Mesothelioma patients showed an impressive immune response to TroVax, a novel cancer vaccine, when it was combined with standard chemotherapy in a recent clinical trial.

Researchers from Cardiff University in the United Kingdom conducted the study that was published by the journal OncoImmunology.

TroVax is a laboratory engineered virus designed to target the human protein 5T4.

A mutated form of 5T4 is found in almost all mesothelioma tumors, including the sarcomatoid subtype, the most difficult to treat.

The phase II clinical trial produced a disease control rate of 87 percent, more than double the rate of a previous study done without the vaccine. More than 17 percent of patients saw tumor reduction.

“This was a proof-of-concept study, and we proved it. We were able to demonstrate the response,” Angela Casbard, senior research fellow in statistics at Cardiff, told The Mesothelioma Center at Asbestos.com. “We don’t know yet the clinical impact or what it could be.”

Vaccine Used with Other Cancers

TroVax, which is produced by Oxford BioMedica in the United Kingdom, already has been tested successfully with renal, colorectal and prostate cancers. Treatment-related side effects were comparable to those seen with chemotherapy alone.

Of the 23 patients who received at least three doses of TroVax, 22 developed a humoral or cellular immune response.

This was well beyond the targeted response rate of 64 percent.

All three patients with sarcomatoid mesothelioma showed an immune response.

“I would not say ‘yes’ [it has real potential as a treatment option] because we were only looking for immune response at this point, which we got,” Casbard said. “To affect the outcome [for a patient], or prevent development [of the disease], that may be possible, but it wasn’t something we were looking for.”

The study was conducted at the Velindre Cancer Center at Cardiff. First-line patients, with locally advanced or metastatic mesothelioma, were eligible for nine intramuscular injections of the drug.

Vaccine Started Before Chemotherapy

The first injection came two weeks before chemotherapy began and continued at regular intervals.

The median progression-free survival was 6.8 months. The median overall survival was 10.9 months.

Only 16 patients received all nine injections.

Reasons for stopping before nine injections included death, adverse effects, disease progression and opting for surgery instead. The average age of patients in the study was 66.

The chemotherapy regimen was a combination of pemetrexed (Alimta) and cisplatin.

Eight of the patients were still alive after 24 months, a percentage that exceeded previous studies using only chemotherapy. Fifteen patients died within 14 months of starting the trial.

Looking to Improve Chemotherapy Effectiveness

Researchers are searching for ways to improve the effectiveness of chemotherapy, which remains the only FDA-approved treatment for mesothelioma.

Various immunotherapy agents are being tested in trials, many in combination with chemotherapy.

A few have shown real potential, but only in a select group of patients.

Keytruda (pembrolizumab) and Opdivo (nivolumab) have been approved for certain cases of lung cancer. Their success with mesothelioma — used mostly in clinical trials — has been sporadic.

Recent study authors have endorsed more testing of TroVax, but details for the next trial are still pending.

“In this phase II trial, TroVax with pemetrexed-cisplatin chemotherapy showed robust immune activity, acceptable safety and tolerability to warrant further investigation in a phase III setting,” the authors wrote.

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