Doctors at the Princess Margaret Cancer Center in Toronto are studying the use of hypofractionated radiation to increase the effectiveness of immunotherapy for patients with mesothelioma.
They are expected to launch soon a clinical trial that will add an immunotherapy combination to the high-dose radiation and aggressive surgery mix that has been so successful in Toronto.
“There are a lot of questions that still need to be answered, but if I was a betting man, I’d lay odds on it [working well],” Dr. John Cho of the cancer center’s clinical research unit, told The Mesothelioma Center at Asbestos.com. “It’s all very promising.”
Cho has been working closely with thoracic surgeon and mesothelioma specialist Dr. Marc de Perrot at Toronto General Hospital.
Perrot was the lead author of an editorial published recently by the Journal of Thoracic Disease, suggesting the radiation and immunotherapy combination could become standard of care for pleural mesothelioma patients.
“Our group demonstrated that non-ablative, hypofractionated radiation can also have a major impact on the immune system in mesothelioma,” Perrot wrote. “Hence, the combination of non-ablative hypofractionated radiation with targeted immunotherapy is a promising strategy for the near future in mesothelioma.”
SMART Evolves into SMARTER
The research team in Toronto is continuing to build on its unconventional Surgery for Mesothelioma After Radiation Therapy (SMART) approach that has achieved unprecedented success.
Researchers reported a three-year survival rate of 66 percent among patients with no lymph node involvement and the epithelial subtype. They also estimated disease-free survival at 47 months and median overall survival at 51 months.
The high-dose radiation before surgery is a reversal of the traditional order of treatment at most specialty centers in the United States.
Most multimodal treatment for mesothelioma starts with chemotherapy, which is followed by aggressive surgery and finishes with radiation, if it even is used at all.
The high-dose radiation administered first is used only with the radical extrapleural pneumonectomy surgery, which removes an entire lung, eliminating the option of a lung-sparing pleurectomy and decortication.
Researchers in Toronto considered a protocol that combined immunotherapy with the SMART approach. But the recent trend among surgeons favoring the P/D instead of the EPP changed the thinking.
They will open a study soon called Surgery for Mesothelioma After Radiation Therapy using Extensive pleural Resection, or SMARTER.
Finding the Perfect Dose
SMARTER will include a less-toxic, pre-surgery radiation that will work with either the P/D or the EPP.
Once a safe and effective level of radiation is found, the trial will move into a second phase to include the immunotherapy drugs.
“In simplistic terms with radiation, there is going to be a sweet spot there, but you just don’t know where it is right now,” Cho said. “If the dosage is too low, it doesn’t do much in terms of killing the cancer cells, but too much radiation can be immunosuppressive.”
In the past, traditional radiation therapy is given mostly in a palliative setting. Higher-dose, hypofractionated radiation — which is completed in a much shorter period — has shown an ability to spark activation of the immune system against cancer tumors.
Previous lung cancer studies have shown it can increase the effectiveness of certain immunotherapy drugs.
Future of Cancer Care
While most oncologists believe immunotherapy is the future of cancer care, current immunotherapy drugs have been inconsistent.
Their effectiveness has been selective and hard to sustain, prompting the effort to improve their consistency.
“Immunotherapy is real. It’s going to change the paradigm of how we treat patients,” Cho said. “This is the first time in many years that we have what appears to be an effective agent.”
Although no immunotherapy drug has been approved by the FDA for use with mesothelioma, select patients are receiving them — and some benefiting — through clinical trials or special-use exceptions.
Keytruda (pembrolizumab) and Opdivo (nivolumab) already have been approved for non-small cell lung cancer. They have been effective for some mesothelioma patients, but not for others.
Yervoy (ipilimumab) and Tecentriq (atexolizumab) also have shown inconsistent effectiveness with different cancers.
“It may turn out there’s not one solution that fits everybody. Everyone’s immune system is different,” Cho said. “Immunotherapy is here to stay, but the question is how to integrate it with therapies we already have. What we’re doing now could be a real game changer.”