A leading hypothesis for why adding immunotherapy to chemoradiation failed is that radiation, particularly for central tumors, destroys the very lymphocytes immunotherapy aims to activate. This biological mechanism suggests the radiation essentially canceled out the drug's intended effect.
The failure of the concurrent chemo-immuno-radiation approach has not stalled progress. Instead, new clinical trials are actively exploring novel strategies like SBRT boosts, dual checkpoint inhibitors, radiosensitizing nanoparticles, and induction immunotherapy to improve upon the current standard of care.
While the feared side effect of severe lung inflammation (pneumonitis) did not increase, other immune-mediated adverse events did. This led to higher rates of treatment discontinuation in the experimental arm, potentially negating any benefits of the concurrent approach and contributing to the trial's failure.