Pattern of failure in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy with/without immune checkpoint inhibition.

Abstract

e20570 Background: We compared pattern of failure in patients treated with chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (IO, immuno-oncology therapy) and CRT alone for inoperable stage III NSCLC. Methods: Prospective data of thirty nine consecutive patients who completed CRT-IO with sequential durvalumab (72%, 28 patients) or concurrent and sequential nivolumab (28%, 11 patients) and a sensitive propensity score matched (PSM adjusted for patients age, gender, T- and N-status, PTV, histology) cohort of 39 patients treated with CRT alone were analyzed. First site of failure was compared between the CRT-IO and the CRT alone subgroup. Results: All patients were treated with conventionally fractionated thoracic irradiation to a total dose of at least 60Gy (range: 60-66Gy), all patients received either sequential or simultaneous chemotherapy while 95% (74 patients; CRT-IO: 38/39; CRT alone: 36/39) received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 33.3 (range: 1.5-102.9) months; median overall survival (OS) was 34.9 (95%CI: 10.7-59.1) months (CRT-IO: not reached; CRT alone: 24.4, p = 0.003); median progression-free survival (PFS) was 13.6 (95% CI: 10.5-6.7) months (CRT-IO: 26.3; CRT alone: 8.3; p < 0.001). At the time of evaluation 21 (53.8%) vs. 7 (17.9%) patients of the CRT-IO vs. CRT alone subgroup were progression free and alive (p = 0.003); 4 (10.3%) vs. 3 (7.7%) had brain metastases as first site of failure; 7 (17.9%) vs. 6 (15.4%) had ≤ 3 extracranial metastasis and 3 (7.7%) vs. 4 (10.3%) had multi-organ progression. Local-regional recurrence (LRR) as first site of failure was significantly less frequent in patients treated with CRT-IO vs. CRT alone, namely 3 (7.7%) vs. 12 (30.8%) patients (p = 0.001); median time to LRR was not reached vs. 15.0 (95%CI: 0.9-33.7) months. Conclusions: Pattern of failure differ significantly in patients treated with CRT-IO vs. CRT alone; CRT-IO patients are significantly less likely to develop a LRR. No differences in the prevalence of brain metastases as first site of failure could be detected.