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Lung cancer is a focus of radioimmunotherapy research and development. There are currently at least 8 phase 1 and phase 2 clinical trials evaluating radiotherapy or chemoradiation plus a PD-1/PD-L1 immune checkpoint blockade agent, pembrolizumab or nivolumab, in patients with NSCLC.12
Toxicities
Educating patients about the possible risks and toxic symptoms associated with radioimmunotherapy regimens will fall largely to oncology nurses, as will monitoring patients against the emergence of adverse events, which in some cases must be detected and managed quickly to avoid potentially life-threatening events.
A 2017 systematic review of data from 49 clinical studies of concurrent stereotactic radiotherapy (SRT) and targeted therapies or immunotherapies, including 8 retrospective studies and case reports of ipilimumab radioimmunotherapy, found that the available evidence base suggests these treatments are well tolerated when deployed against brain metastases.4 However, it should be emphasized that most of the studies in this review described results for patients with brain metastases.4 The 6 retrospective studies of SRT plus concurrent CTLA-4 checkpoint blockade with ipilimumab in patients with melanoma brain metastases found that at median doses ranging from 14 to 60 Gy in 1 to 5 radiation fractions, SRT plus ipilimumab did not increase toxicity risks over ipilimumab immunotherapy alone.4 Grade 3 toxicities included pruritus, hepatitis, diarrhea, pyrexia, nausea, fatigue, anorexia, skin reactions, endocrine reactions, and GI toxicities; one patient suffered grade 4 cardiopulmonary toxicity.4 Among reported toxicities were also grade 3 seizures and CNS hemorrhages attributable to SRT itself, rather than the combined radioimmunotherapy.4
Less is currently known about PD-1/PD-L1 immune checkpoint blockade plus radiotherapy, although several clinical trials are now under way.4,10,12 Studies representing 27 patients receiving nivolumab plus SRT reported 2 cases of grade 3 cerebral edema and 1 case of grade 4 cerebral edema.4 As mentioned above, there are at least 8 phase 1 and 2 clinical trials under way for PD-1/PD-L1-blockade radioimmunotherapy in patients with NSCLC.12 Findings from those studies, once reported, should cast much-needed new light on toxicity risks.
The authors of the 2017 systematic review cautioned that even as concurrent SRT immunotherapy and targeted therapies become more widely used, little is yet known about the safety profiles of these combination regimens.4 They called for prospective registry databases to standardize and improve reporting of toxicities. 4
References
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