Immune to dose constraints.

Top Line: Definitive radiation for very locally-advanced non-small cell lung cancer is dosimetrically challenging.

The Study: The landmark Checkmate 816 trial established neoadjuvant chemoimmunotherapy significantly improves outcomes when proceeding to surgery, particularly among the most advanced cases. Shouldn’t this strategy theoretically help for bulky cases prior to definitive chemoradiation..? Here’s a retrospective series to start providing answers. It analyzes 75 patients receiving upfront chemoimmunotherapy prior to definitive chemoradiation for bulky (primary tumor ≥ 5 cm nodes ≥ 2 cm) unresectable stage III NSCLC. Induction consisted of platinum-based chemo coupled with any one of six PD1-axis inhibitors for a median of 4 cycles. Over 3 out of 4 patients achieved an objective response during the induction phase. Now to the real headline: median progression-free survival (PFS) was an eyebrow-raising 31 months—that’s approaching double the median PFS of 17 months seen with consolidative immune checkpoint inhibition (ICI) on the backend of the blockbuster PACIFIC trial. What’s more, the patients who received further consolidative ICI (n=28) had an even higher rate of overall survival at two years (86% v 64%). Granted, this is a small retrospective study and the numbers are too small for statistical significance. Of note, despite clear dosimetric advantages due to reduced target volume, grade 3 pneumonitis was higher here (9%) than seen in PACIFIC (4%), presumably due to having ICI on board at time of radiation. A final important consideration is that this is a retrospective selection of only patients who proceeded from induction immunochemotherapy to definitive chemoradiation and thus does not include anyone who may have decompensated during the induction phase.

TBL: Induction chemoimmunotherapy prior to definitive chemoradiation for bulky NSCLC is an intriguing approach deserving of prospective evaluation, as well as a commonsense alternative if upfront radiation is not dosimetrically feasible. | Wang, Int J Radiat Oncol Biol Phys 2023