Session Item

Immune checkpoint inhibition (ICI) has changed oncologic treatment strategies dramatically. Both monotherapy and combination therapies have established themselves not only in the metastatic situation to optimize the effect on the tumor. Radiotherapy (RT) is a highly effective local treatment. Especially local but also systemic adverse events due to RT are well known. The mechanisms by which RT and ICI synergistically modulate the immune response might also affect treatment-related side effects. Severe adverse events due to ICI (CTCAE v.5.0 Grade 3-4) are reported in 17-21% of the patients receiving monotherapy. In this study we retrospectively analyzed patients being treated with PD-1 inhibitors (PD-1i) alone or with additional RT regarding the tolerability of this combination concept.

We screened all patients treated with PD1i at our center between 2013 and 2017 and divided the patients into 2 different treatment groups with (RIT = radio-immunotherapy) or without (IT = immunotherapy alone) additional RT. We collected baseline characteristics, PD1i and RT details, as well as toxicities. Patient characteristics and adverse events were compared by Kruskal-Wallis-test for continuous variables and Pearson''s chi-square test for categorical variables.

201 patients with different types of malignancies (62.5% malignant melanoma; 18.5% non-small cell lung cancer; 7% renal cell carcinoma; 19% others) could be analyzed. We obtained a median follow up period of 22.3 months until 12/2017. Patients received at least 3 cycles of either pembrolizumab (n=112) or nivolumab (n=89). 153 patients received additional RT. Regarding the incidence of toxicities the most frequent adverse events in the RIT group were fatigue (47.2%) and skin toxicities (45.5%) followed by abdominal (33.3%) and lung (21.8%) problems. In the IT group, most frequent side effects were lung toxicities (19.6%) followed by skin toxicities (18.4%), fatigue (17.6%) and abdominal problems (16.3%). In total, more toxicities were reported when adding RT (8.5% vs 19.4%). The expected IT-related adverse events like lung, thyroid and liver toxicities did not differ statistically significantly in between both treatment groups. At least 1 maximum-grade 3 or 4 adverse event of any cause occurred in 11.5 % of the patients in the IT group and in 6.9 % of those in the RIT group, including 1 grade 4 event (2.1%) in the IT group and 6 grade 4 events (3.9%) in the RIT group.

Patients being treated with radiotherapy and PD-1 inhibitors tend to have more side effects when compared to those receiving PD-1 inhibitors alone. Regarding immunotherapy-related adverse events we observed no statistically significant higher numbers when patients are also treated with RT. The reported higher numbers are most likely due to the side effects of the RT itself. With a rare incidence of grade 3 or 4 toxicities the combination treatment of RIT can be applied safely in clinical routine.