Checkpoint inhibitor consolidation after definitive chemoradiation for stage III non–small cell lung cancer: Real-world experience in a large academic health system.
Authors: Yegya-Raman Nikhil , Friedes Cole , Sun Lova , Marmarelis Melina Elpi , Levin William C. , Cengel Keith A. , Lally Brian , Davella Christopher , Kosteva John A. , Singh Aditi Puri , Cohen Roger B. , Aggarwal Charu , Ciunci Christine , Berman Abigail T. , Langer Corey J. , Feigenberg Steven J. 
Published: June 2022

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Background: The PACIFIC trial demonstrated a 10% improvement in 5-year survival with the addition of consolidation durvalumab versus placebo after chemoradiation (CRT) in good performance status patients (pts) with stage III non-small cell lung cancer (NSCLC). However, not all patients who complete CRT go on to receive consolidation durvalumab. We sought to describe real-world use of consolidation durvalumab or other immune checkpoint inhibitors (ICI) in this setting within a single academic health system. Methods: We retrospectively identified pts with unresectable stage III NSCLC treated with definitive CRT between October 2017 and October 2020 within the University of Pennsylvania Health System, including two urban hospitals and two satellite centers. Pts either received consolidation ICI (ICI group) or did not (no ICI group). Baseline characteristics of the groups were compared with the Chi-squared, Fisher exact, or Wilcoxon rank-sum test as appropriate. Overall survival (OS), measured from the last day of CRT, was compared using the Kaplan-Meier method and log-rank test. Results: Of the 148 consecutively treated pts who completed CRT, 108 (73%) received consolidation ICI; 40 (27%) did not. Within the ICI group, 42% completed 1 year (yr) of treatment. Within the no ICI group, reasons for non-receipt included disease progression (n = 14, 35%), CRT toxicity (n = 7, 18%), comorbidity or decline unrelated to CRT (n = 7, 18%), provider choice (n = 6, 15%) due to EGFR mutation (n = 5) or atypical histology (n = 1), pt refusal (n = 3, 8%), and death without progression (n = 3, 8%). The ICI group had better performance status (ECOG 0/1/2, 46%/49%/5% ICI vs 25%/48%/28% no ICI, p < 0.001) lower Charlson Comorbidity Index (median, 5 [IQR 4-6] ICI vs 6 [IQR 5-8] no ICI, p = 0.02), and lower rates of active autoimmune disease or immunosuppression (5% ICI vs 15% no ICI, p = 0.03). There were no differences between groups in age (median, 68 yrs [IQR 63-73] ICI vs 71 yrs [IQR 65-73] no ICI, p = 0.25), sex (female, 60% ICI vs 50% no ICI, p = 0.27), race (Black, 19% ICI vs 20% no ICI, p = 0.82), stage (IIIA/B/C, 42%/48%/11% ICI vs 40%/50%/10% no ICI, p = 0.96), and PD-L1 expression ( < 1%/1-50%/ > 50%/unknown, 36%/25%/29%/10% ICI vs 40%/25%/28%/8% no ICI, p = 0.97). 1- and 2-yr OS were 83% and 61% in the ICI group versus 52% and 34% in the no ICI group, respectively (p < 0.001). Within the no ICI group, OS was worse among those with versus those without disease progression (PD) post-CRT (1-yr OS 24% vs 74%, p = 0.03). Conclusions: In this retrospective study within a large academic health system, we found that over one-quarter of pts who completed chemoradiation for stage III NSCLC did not receive consolidation ICI, most commonly due to disease progression, CRT toxicity, or comorbidity. Survival amongst these pts is particularly poor, especially for those who experience PD shortly after CRT.