I Combinator

Top Line: In an attempt to upgrade “clinically notable” to “statistically significant,” here’s a pooled analysis of two randomized phase 2 trials evaluating the systemic impact of adding radiation to immune checkpoint inhibition (ICI) for metastatic non-small cell lung cancer (NSCLC).

The Study: Enrollees in both trials, PEMBRO-RT (n=76) and one from MDACC (n=72), received pembrolizumab initiated either concurrent to or within one week of completion of radiation. In PEMBRO-RT, radiation was ablative (24 Gy / 3) and directed at only one site. In the MDACC trial, radiation was directed at all sites when feasible, including resorting to conventional fractionation (45 Gy/ 15) if needed, though ablative dosing (50 Gy / 4) was preferred. When results were pooled, the doubling of median progression-free survival with the addition of radiation did indeed become “significant” (4.4 → 9 months). What’s more newsworthy (yet really shouldn’t be shocking at this point)? Median overall survival was also more than doubled with this randomized intervention (8.7 → 19.2 months). What can explain this, particularly in the setting of irradiating only one of many lesions? The authors did find that non-irradiated lesions were more likely to respond with (42%) compared to without (20%) radiation (invoking the abscopal effect). But we also have to remember that progression on immunotherapy is often heterogeneous among sites--and that ablation of dominant lesions may lead to better overall disease control.

TBL: More randomized evidence supports the hypothesis that radiation is synergistic with ICI for NSCLC. | Theelen, Lancet Respir Med 2020

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