Abscopal absence.

We’re all familiar with the speculation of synergy when radiation is combined with immune checkpoint inhibition (ICI). Despite well-deserved hype surrounding the use of ICI for non-small cell lung cancer (NSCLC), the hard truth is that many patients with metastatic disease fail to respond. This phase 2 trial of 90 patients with metastatic NSCLC progressing after first-line PD(L)-1 targeted therapy included three arms: [1] durvalumab with tremelimumab (CTLA-4 inhibitor) alone or [2] with hypofractionated radiation 8 Gy x 3 = 24 Gy or, and here’s where things get interesting, [3] with low-dose radiation 0.5 Gy twice daily x 2 days with each infusion for a total of 8 Gy. The target could be any 1-2 gross tumors, but the protocol encouraged prioritizing progressive lesions, preferably in liver or lung. In the end, the primary endpoint of response rate outside irradiated lesions left much to be desired, at rates of 2-3 out of 26 in each arm. Finally, there were plenty of exploratory analyses, but perhaps most interesting was notable decreases in peripheral percent lymphocyte counts following radiation that was associated with progression. | Schoenfeld, Lancet Oncol 2022