Risk of Pneumonitis in Patients With Stage III Non-Small Cell Lung Cancer Treated With Definitive Chemo-RT and Durvalumab Consolidation

Purpose/Objective(s)The PACIFIC Trial established durvalumab consolidation after definitive chemo-radiation (CRT) as the standard of care for Stage III Non-small cell lung cancer (NSCLC) in those not undergoing surgery. The rate of G3+ pneumonitis risk in this trial was less than 5% in the durvalumab arm. However, there is limited data regarding radiotherapy (RT) lung dosimetry from the PACIFIC trial to determine whether it accurately reflect real-world patients with locally advanced NSCLC who often require high lung dose to obtain target coverage. It is unclear whether established constraints accurately predict pneumonitis risk in this population. We aim to report outcomes and pneumonitis risk in a real word population of patients treated with CRT and durvalumab and determine risk of pneumonitis based on RT lung dosimetry.Materials/MethodsWe identified patients treated with CRT and durvalumab at a single institution for NSCLC not undergoing surgical resection. Patients were excluded if RT dosimetry was not available. NCI CTCAE v5.0 was used for grading pneumonitis. Differentiation of radiation pneumonitis (RP) vs durvalumab pneumonitis (DP) was determined by a radiation oncologist. Kaplan-Meier method was used to analyze overall survival (OS), progression free survival (PFS), and pneumonitis incidence and were compared using log rank test.Results40 patients treated with CRT and consolidative durvalumab were identified with median follow-up of 19 months. 90% of patients were Stage IIIA or IIIB (IIA-IIIC). Median RT dose was 63 Gy (54-70 Gy). Median MLD was 16 Gy (7-21 Gy). Median lung V20 was 29.5% (10%-38%). OS and PFS at 2 years was 69.7% was 60.3% respectively. Grade 2+ and 3+ combined RP and DP for the overall cohort was 29.0% and 24.0% respectively. Median time to pneumonitis from completion date of RT was 129 days. 22.5% (9/40) of patients required steroids for treatment of pneumonitis. 15% (6/40) of patients had a new O2 requirement attributed to pneumonitis. Pneumonitis led to discontinuation of durvalumab in 20% (8/40) of patients. Of the 9 cases of pneumonitis, 7 (77.8%) were consider RP, and 2 (22.2%) DP. Grade 2+ pneumonitis risk was 64.5% in patients with lung V20 > 30% versus 8.3% in patients with lung V20 ≤ 30% (P > 0.001). Grade 2+ pneumonitis risk was 59.4% in patients with a MLD > 17 Gy versus 8.3% in those with MLD ≤ 17 Gy (P < 0.001). Grade 3+ pneumonitis risk was 51.5% in patients with lung V20 > 30% versus 8.3% in patients with lung V20 ≤ 30% (P = 0.003). Grade 3+ pneumonitis risk was 47.0% in patients with a MLD > 17 Gy versus 8.3% in those with MLD ≤ 17 Gy (P < 0.005).ConclusionRisk of pneumonitis in this single institution study of real-world patients treated with definitive CRT and durvalumab was higher than reported the PACIFIC trial. Pneumonitis risk was markedly elevated in patients with lung V20 > 30% or MLD > 17 Gy. Larger series are needed to determine optimal dose constraints in this patient population in the era of durvalumab. The PACIFIC Trial established durvalumab consolidation after definitive chemo-radiation (CRT) as the standard of care for Stage III Non-small cell lung cancer (NSCLC) in those not undergoing surgery. The rate of G3+ pneumonitis risk in this trial was less than 5% in the durvalumab arm. However, there is limited data regarding radiotherapy (RT) lung dosimetry from the PACIFIC trial to determine whether it accurately reflect real-world patients with locally advanced NSCLC who often require high lung dose to obtain target coverage. It is unclear whether established constraints accurately predict pneumonitis risk in this population. We aim to report outcomes and pneumonitis risk in a real word population of patients treated with CRT and durvalumab and determine risk of pneumonitis based on RT lung dosimetry. We identified patients treated with CRT and durvalumab at a single institution for NSCLC not undergoing surgical resection. Patients were excluded if RT dosimetry was not available. NCI CTCAE v5.0 was used for grading pneumonitis. Differentiation of radiation pneumonitis (RP) vs durvalumab pneumonitis (DP) was determined by a radiation oncologist. Kaplan-Meier method was used to analyze overall survival (OS), progression free survival (PFS), and pneumonitis incidence and were compared using log rank test. 40 patients treated with CRT and consolidative durvalumab were identified with median follow-up of 19 months. 90% of patients were Stage IIIA or IIIB (IIA-IIIC). Median RT dose was 63 Gy (54-70 Gy). Median MLD was 16 Gy (7-21 Gy). Median lung V20 was 29.5% (10%-38%). OS and PFS at 2 years was 69.7% was 60.3% respectively. Grade 2+ and 3+ combined RP and DP for the overall cohort was 29.0% and 24.0% respectively. Median time to pneumonitis from completion date of RT was 129 days. 22.5% (9/40) of patients required steroids for treatment of pneumonitis. 15% (6/40) of patients had a new O2 requirement attributed to pneumonitis. Pneumonitis led to discontinuation of durvalumab in 20% (8/40) of patients. Of the 9 cases of pneumonitis, 7 (77.8%) were consider RP, and 2 (22.2%) DP. Grade 2+ pneumonitis risk was 64.5% in patients with lung V20 > 30% versus 8.3% in patients with lung V20 ≤ 30% (P > 0.001). Grade 2+ pneumonitis risk was 59.4% in patients with a MLD > 17 Gy versus 8.3% in those with MLD ≤ 17 Gy (P < 0.001). Grade 3+ pneumonitis risk was 51.5% in patients with lung V20 > 30% versus 8.3% in patients with lung V20 ≤ 30% (P = 0.003). Grade 3+ pneumonitis risk was 47.0% in patients with a MLD > 17 Gy versus 8.3% in those with MLD ≤ 17 Gy (P < 0.005). Risk of pneumonitis in this single institution study of real-world patients treated with definitive CRT and durvalumab was higher than reported the PACIFIC trial. Pneumonitis risk was markedly elevated in patients with lung V20 > 30% or MLD > 17 Gy. Larger series are needed to determine optimal dose constraints in this patient population in the era of durvalumab.