P82.04 Adaptive Radiation Therapy with Consolidation Sintilimab in Stage III NSCLC: Challenges in Recruiting Patients for Adjuvant Immunotherapy

Abstract

The PACIFIC reported a significantly improved overall survival for consolidative durvalumab after chemoradiotherapy in unresectable stage III non-small cell lung cancer (NSCLC) in 2018. However, the details in the exclusion of patient enrollment were not reported. It is unclear what proportion of patients after chemoradiotherapy would be eligible to receive immunotherapy. In this study, we aimed to recruit all for consolidation sintilimab, an anti-PD-1 antibody, after definitive chemoradiotherapy using adaptive radiotherapy which can target to the shrunk tumor to reduce the dose to surrounding normal tissues and decrease the toxicities. This was a single-arm prospective phase II trial (CARTAI; NCT03732430). Patients with histologically confirmed NSCLC, unresectable stage III medically fit for concurrent chemoradiotherapy were eligible. Radiation therapy was delivered using mid-treatment CT guided adaptive IMRT. Sintilimab was given within 45 days after completion of RT, when patients had grade 1 or less acute toxicity, with ECOG PS 0 or 1, adequate hematologic, liver and kidney function. Any patients who had unresolved grade 2 or higher toxicity were excluded from enrollment. The prescription doses of radiotherapy were 64-66Gy to the GTV and 54Gy to the PTV in 30 fractions, unless exceeding the dose constraints. The patents were intravenously given sintilimab, an anti-PD-1 antibody, 200mg q3w. We initially screened potential patients before the radiotherapy and all interested patients were treated consistently with adaptive RT. Final written consent was obtained, and eligibility was confirmed after completion of radiotherapy. From November 2018 to December 2019, after the initial screening, 107 consecutive patients potentially eligible received concurrent chemoradiation received adaptive IMRT. Eight-eight patients failed for enrollment of consolidation sintilimab. In which, seventy (80%) patients refused to participate the study at the last minutes. Eighteen of 88 (20%) did not meet the inclusion criteria after the end of radiotherapy. main ineligible reasons were grade 2 or higher toxicities, including radiation-induced pneumonitis in 7 patients, unresolved esophagitis in 5, 2 developed both, and 2 with unresolved leukopenia. A total of 19 patients (17.8%) consented to participate in the adjuvant immunotherapy. Four of them (21.5%) were found ineligible, including 2 patients with grade 2 radiation pneumonitis, 1 with esophagitis, and 1 with leukopenia. There were finally 15 patients (78.9%) enrolled in this study. This study found approximately twenty percent of all consented and refused patients were ineligible to receive consolidative immunotherapy after the end of concurrent chemoradiotherapy. The main barrier for eligibility was the radiation-induced acute toxicities, especially pneumonitis and esophagitis.