In their trial, Altorki et al wanted to assess whether radiotherapy would act as an immunomodulator and augment the effectiveness of durvalumab, a monoclonal antibody and immune checkpoint inhibitor that binds to the protein PD-L1, preventing PD-L1 from binding the PD-1 protein on T cells. The researchers enrolled 60 patients with potentially resectable, early-stage non–small cell lung cancer (NSCLC) with an Eastern Cooperative Oncology Group performance status of either 0 or 1.

One group of patients was randomly assigned to receive a regimen of neoadjuvant durvalumab monotherapy (two cycles of 1.12 g IV infusion over 60 minutes), while the other group was treated with neoadjuvant durvalumab plus stereotactic body radiotherapy (SBRT). Although the durvalumab cycles were equal for both groups, the second group received SBRT administered as three consecutive, daily fractions of 8 Gy (a derived unit of ionizing radiation dose) delivered to the primary tumor immediately before the first cycle of durvalumab. The researchers discovered that major pathological response was detected in two (6%-7% [95% CI 0.8–22.1]) of 30 patients in the durvalumab-monotherapy group and 16 (53.3% [34.3–71.7]) of 30 patients in the durvalumab-plus-radiotherapy group.

The difference in major pathological response rate between both groups was substantial (crude odds ratio 16.0 [95% CI 3.2-79.6]; P <.0001). In the 16 patients in the dual-therapy group with a major pathological response, eight (50%) had a complete pathological response. The second cycle of durvalumab was suspended in three (10%) of 30 patients in the dual therapy group due to immune-related adverse events (grade 3 hepatitis, grade 2 pancreatitis, and grade 3 fatigue and thrombocytopenia).

Additionally, grade 3 to 4 adverse events occurred in five (17%) of 30 patients in the durvalumab-monotherapy group and 6 (20%) of 30 patients in the durvalumab-plus-radiotherapy group. The most frequent grade 3 to 4 events were hyponatremia (three [10%] patients in the durvalumab monotherapy group) and hyperlipasemia (three [10%] patients in the durvalumab-plus-radiotherapy group). Two patients in each group had serious adverse events (pulmonary embolism [n = 1] and stroke [n = 1] in the durvalumab-monotherapy group, and pancreatitis [n = 1] and fatigue [n = 1] in the durvalumab-plus-radiotherapy group). The researchers also noted that there were no treatment-related deaths or deaths within 30 days of surgery.

The authors of the study concluded that the neoadjuvant regimen of durvalumab plus SBRT was correlated with "a significant improvement in major pathological response" and that the treatment also appeared to be well-tolerated and safe. The researchers noted that it is "not possible to completely dismiss the possibility that radiotherapy alone might have contributed to the observed treatment effect" but concluded that that was "unlikely." In fact, they stated that their discoveries indicate a potential synergistic effect between immune checkpoint blockade and radiation therapy. They concluded that "Despite the small sample size, the robust and better than expected effect size between the groups in major pathological response is promising and merits confirmation in a larger trial."

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