Durvalumab after concurrent chemotherapy and high-dose radiotherapy for locally advanced non-small cell lung cancer

Abstract

The standard of care for stage III non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by durvalumab. Although doses higher than 66 Gy are standard in our center, they were used in only 6.9% of patients in the PACIFIC trial. We report our experience with durvalumab after high-dose radiotherapy. The database of a tertiary hospital for patients with stage III NSCLC who were treated with CRT and adjuvant durvalumab was evaluated. Progression-free survival (PFS), overall survival (OS), and local-regional failure (LRF) were measured from the administration of durvalumab. Thirty-nine patients were included. All were treated with intensity-modulated radiation (mean dose 69.9 Gy); Median follow-up time was 20.4 months (range 1–35.4). At 12 months, PFS was 49%, OS 79%, and LRF 14%. Intrathoracic failure at first progression was demonstrated in 8 (21%) patients. Adverse events requiring corticosteroids occurred in 10(25.6%) patients: pneumonitis – 6 (15.4%), hepatitis – 2 (5.1%), and arthralgia and pericarditis – 1 (2.6%). One patient (2.6%) died of pneumonitis. The occurrence of pneumonitis was significantly associated with lung V5 (55% vs. 42%, p = .04) and V20 (28% vs. 19%, p = .01) and mean lung dose (14.8 Gy vs.11.6 Gy, p = .05). The similar 12-month PFS and OS rates of our cohort and the PACIFIC trial support the use of high-dose radiotherapy in patients with stage III NSCLC. Treatment-related mortality was similar to the PACIFIC results. The intrathoracic failure rate in our cohort was lower than that reported from the PACIFIC trial, suggesting that radiation dose escalation may improve local control.

Durvalumab after Sequential High Dose Chemoradiotherapy versus Standard of Care (SoC) for Stage III NSCLC: A Bi-Centric Retrospective Comparison Focusing on Pulmonary Toxicity

“…Although the cohort from this single-center experience was small, the loco-regional relapse rate in these 39 patients could be reduced to 21%. These results imply that dose-escalation in the context of durvalumab consolidation may increase intrathoracic disease control without excess toxicity [26].…”

“…Although the PFS and OS data from the PACIFIC trial present a new milestone in the treatment of stage III NSCLC, the intrathoracic failure rate of 36.6% remains high [25], which may be due to the relatively low total radiation doses of 54 to 66 Gy. Landman et al were the first to successfully address this issue by combining radiation dose-escalation and durvalumab [26]. Although the cohort from this single-center experience was small, the loco-regional relapse rate in these 39 patients could be reduced to 21%.…”

“…Based on these results [26], we hypothesized that durvalumab following sequential high-dose RT can be applied without excess pulmonary toxicity compared to SoC. Therefore, the aim of this retrospective analysis was to evaluate pulmonary toxicity in patients treated with durvalumab maintenance after sequential high-dose radiochemotherapy compared to SoC concomitant CRT.…”

Modified VMAT Plans for Locally Advanced Centrally Located Non-Small Cell Lung Cancer (NSCLC)

“…The effect could be obvious for patients who planned to receive immunotherapy after chemoirradiation. The non-PTV lung dose of our H-VMAT resulted in a V5 of 49.29% ± 9.51; V20 of 21.83% ± 4.26 and mean lung dose of 13.19 Gy ± 2.47, which was lower than the threshold that patients developed pneumonitis at in Landman et al's 2021 study [24]. Thus, by controlling the non-PTV lung dose, the progression-free survival would be improved by the application of immunotherapy while limiting the risk of developing pneumonitis.…”

“…V5 less than 65% and V20 less than 25% were identified as threshold of grade 2 radiation pneumonitis [23]. With the application of immunotherapy (Durvalumab) after chemoirradiation, the constraints were even tightened, with V5 less than 55%, V20 less than 23% and mean lung dose less than 14.8 Gy [24]. In this study, among all lung DV parameters, the non-PTV lung was optimized based on the dose constraints only.…”