113P Proton-therapy and concurrent chemotherapy in stage III NSCLC: Effects on durvalumab eligibility and safety profile

Abstract

Concurrent chemo-radiotherapy (CCRT) followed by adjuvant Durvalumab (D) represents standard of care for patients (pts) with unresectable stage III NSCLC. The RT can be delivered with both protons and photons. An earlier start of adjuvant D after CCRT may lead to better outcome. Little is known about the effects of protons on adjuvant D efficacy and safety. We assessed whether intensity modulated proton therapy (IMPT), compared to intensity modulated photon therapy (IMRT) affects eligibility for D (primary endpoint) and immune related adverse events (IRAEs) (secondary endpoint) in pts with stage III NSCLC treated with CCRT and adjuvant D. Retrospective data completion and analysis of a 2-center prospectively collected series of pts with stage III NSCLC, receiving CCRT between 06.16 and 02.21, staged with FDG-PET and brain imaging. Main exclusion criteria were previous cancer diagnosis-within 2 years- and thoracic RT. A list of 226 pts was collected, 67 pts received adjuvant D and were included (IMPT: n=28, IMRT: n=39). Median age was 66 years, 52% were male, 33% had a squamous NSCLC and 42% had a WHO Performance Status (PS) of 0 before CCRT. All pts received 60-64 Gy of RT. Programmed death-ligand 1 (PDL-1) level was available for 76% of pts and 39% had a PDL-1 ≥ 50% (no significant differences between IMPT and IMRT). At day 21 after CCRT, 93% (IMPT) vs 72% (IMRT) treated pts had a PS≤1 (Odds Ratio 0.8, 95% CI: 0.67-0.95, p=0.03). The median time from the end of CCRT and start of D was 32 vs 38 days respectively (Not Significant (NS)). IRAEs of any grade were reported in 21% versus 31% of pts treated with IMPT versus IMRT, respectively (NS). Hypothyroidism accounted for 44% of IRAEs. Any grade (grade 3) pneumonitis during D was reported in 25% (7%) of IMPT and 23% (5%) of IMRT (NS). Median follow-up was 19.5 months and 9.5 months for IMRT and IMPT, respectively. 90% of pts were still alive and 73% were disease free. IMPT vs IMRT treated pts received a significantly lower RT dose to bone marrow, heart and lungs. PS at day 21 after CCRT was better in IMPT treated pts, potentially increasing eligibility for adjuvant D. The lower RT dose delivered with IMPT might explain our findings. IMPT appears to be as safe as IMRT regarding IRAEs during D.