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Top Line: Does ipilimumab improve the response to concurrent chemoradiation for stage III NSCLC?

The Study: If you recall ASTRO 2021, you know the answer is no. Adjuvant immunotherapy is standard of care for patients treated with definitive chemoradiation for stage III NSCLC. The next obvious question is whether immunotherapy should be given during chemoradiation. There have been several phase 2 trials testing concurrent PD-1 or PD-L1 inhibitors concurrent with chemoradiation. This trial sought to establish the safety of ipilimumab, a CTLA4 inhibitor, concurrent with chemoradiation followed by maintenance nivolumab for stage III NSCLC. Patients were treated with 60 Gy in 30 fractions and one of three platinum doublet chemo regimens. Ipilimumab was given on week 1 and 4 of treatment. After completing CRT, 12 cycles of maintenance nivolumab were administered. The trial was stopped early after enrolling just 19 patients largely due to a high rate (42%) of grade 3+ pulmonary toxicity. There were 5 grade 5 events (26%) with 3 being possibly treatment related. The observed pulmonary toxicity was despite a very “safe'' median lung V20 of 26.1% and a median mean lung dose of 14.1 Gy. Put another way, it is not clear that standard lung dose constraints are adequate with concurrent immunotherapy and particularly CTLA4 inhibition. While the numbers were small, the highest rate of grade 3+ pulmonary events happened in those receiving carbo/paclitaxel (4 of 5) compared to cis/etoposide (3 of 6) and cis/pemetrexed (1 of 8). In fact, 2 of the 3 grade 5 events occurred in patients receiving carbo/paclitaxel. 

TBL: This phase I study was stopped early due to a high rate of serious pulmonary toxicity when ipilimumab was given with concurrent chemoradiation for stage III NSCLC. | Liveringhouse, Int J Radiat Oncol Biol Phys 2023