Immunotherapy safe within 90 days of radiation therapy for patients with cancer
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Use of an immune checkpoint inhibitor within 90 days of radiation therapy did not increase risk for serious adverse events among patients with cancer, according to a pooled analysis of prospective trial data published in JAMA Oncology.
Rationale
“When new cancer drugs come on the market, they have usually been studied in patients with advanced cancers who have failed prior therapies. Drug study designs generally include a provision that prohibits giving other anticancer therapies within a prescribed time interval before the study drug is to be given, which is often between 2 and 4 weeks,” Mitchell S. Anscher, MD, professor in the department of radiation oncology at Virginia Commonwealth University, told Healio.
“However, for radiation therapy, even if there are no overt side effects present after this ‘washout’ period, there may be ongoing molecular events that could predispose patients to an increased risk for side effects from the administration of new therapies,” Anscher added. “That risk was not well-characterized for immunotherapies, which are being widely used in oncology today, so we wanted to address that question using the FDA database.”
Methodology
Anscher and colleagues assessed whether administration of an immune checkpoint inhibitor within 90 days of radiation therapy increased the risk for serious adverse events among 16,835 patients (56.1% aged younger than 65 years; 62.1% men; 79.7% white) included in 68 prospective trials from the FDA database through December 2019.
Researchers divided patients into two groups — those who received radiotherapy within 90 days of immunotherapy (n = 1,733) and those who did not receive radiotherapy (n = 13,956).
The frequency and severity of adverse events served as the primary outcome.
Key findings
Results showed an average absolute difference in adverse event rates of 1.2%, which ranged from zero percent for neurologic adverse events to 8% for fatigue.
Moreover, researchers observed no differences in grade 3 to grade 4 adverse events between the two groups, with the absolute difference ranging from 0.01% to 2%.
“There did not appear to be a meaningful increase in the risk for toxicity from immune checkpoint inhibitors given to patients within 90 days of receiving radiation therapy compared with patients who had not previously received radiation therapy,” Anscher said. “This finding was true across a wide variety of cancer types and for a wide range of immune checkpoint inhibitors.”
Implications
Immune checkpoint inhibitors have been a major success story in the treatment of many advanced cancers, Anscher said.
“Since radiation therapy is commonly used in patients with cancer, it is important to know that adding immune checkpoint inhibitors to a patient’s treatment regimen shortly after completing radiation therapy appeared safe,” he said. “I would encourage my colleagues at the FDA to study this issue in other oncology drugs as they come on the market and encourage researchers and drug companies to capture more detail about prior radiation therapy given to patients enrolled on FDA clinical trials.”
At the very least, this information should include the body site irradiated, the total dose delivered, the number of treatments and the number of days of treatment delivery, Anscher added.
“We usually did not have this level of detail, and if we had access to this information, it would have improved our study,” he said. “We also need more information about the safety of using radiation therapy and immunotherapy concurrently rather than sequentially.”
Commentary
“This review of the compendium of data from the [FDA] registry provides additional assurances that sequential [radiotherapy] and [immunotherapy] is tolerable and safe. It suggests that when [radiotherapy] leads immunotherapy, the dance goes reasonably smoothly,” Fiyinfolu Balogun, MD, PhD, researcher at Memorial Sloan Kettering Cancer Center, and David Raben, MD, researcher at University of Colorado, wrote in an accompanying editorial.
“The importance of understanding the toxicity from combined [immunotherapy] and [radiotherapy] rises with expansion of immunotherapy to the adjuvant/neoadjuvant setting as it relates to sequencing, volumes treated and the dose per fraction of [radiotherapy],” Balogun and Raben continued. “Further correlatives, such as liquid and radiogenomics, may allow us to move away from ‘one size fits all’ [radiotherapy] doses, which could serve to guide management and trial design decisions.”
References:
Anscher MS, et al. JAMA Oncol.2022;doi:10.1001/jamaoncol.2021.6439.
Balogun F, et al. JAMA Oncol. 2022;doi:10.1001/jamaoncol.2021.6436.
For more information:
Mitchell S. Anscher, MD, can be reached at Virginia Commonwealth University Health, 57 N. 11th St., Richmond, VA 23298; email: mitchell.anscher@vcuhealth.org.
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