Real-world prospective analysis of treatment patterns in durvalumab maintenance after chemoradiotherapy in unresectable, locally advanced NSCLC patients

Abstract

SummaryThe aim of this prospective study is to evaluate the clinical use and real-world efficacy of durvalumab maintenance treatment after chemoradiotherapy (CRT) in unresectable stage, locally advanced non-small cell lung cancer (NSCLC). All consecutive patients with unresectable, locally advanced NSCLC and PD-L1 expression (≥1%) treated after October 2018 were included. Regular follow up, including physical examination, PET/CT and/or contrast-enhanced CT-Thorax/Abdomen were performed every three months after CRT. Descriptive treatment pattern analyses, including reasons of discontinuation and salvage treatment, were undertaken. Statistics were calculated from the last day of thoracic irradiation (TRT). Twenty-six patients were included. Median follow up achieved 20.6 months (range: 1.9–30.6). Durvalumab was initiated after a median of 25 (range: 13–103) days after completion of CRT. In median 14 (range: 2–24) cycles of durvalumab were applied within 6.4 (range 1–12.7) months. Six patients (23%) are still in treatment and seven (27%) have completed treatment with 24 cycles. Maintenance treatment was discontinued in 13 (50%) patients: 4 (15%) patients developed grade 3 pneumonitis according to CTCAE v5 after a median of 3.9 (range: 0.5–11.6) months and 7 (range: 2–17) cycles of durvalumab. Four (15%) patients developed grade 2 skin toxicity. One (4%) patient has discontinued treatment due to incompliance. Six and 12- month progression-free survival (PFS) rates were 82% and 62%, median PFS was not reached. No case of hyperprogression was documented. Eight (31%) patients have relapsed during maintenance treatment after a median of 4.8 (range: 2.2–11.3) months and 11 (range: 6–17) durvalumab cycles. Two patients (9%) developed a local-regional recurrence after 14 and 17 cycles of durvalumab. Extracranial distant metastases and brain metastases as first site of failure were detected in 4 (15%) and 2 (8%) patients, respectively. Three (13%) patients presented with symptomatic relapse. Our prospective study confirmed a favourable safety profile of durvalumab maintenance treatment after completion of CRT in unresectable stage, locally advanced NSCLC in a real-world setting. In a median follow-up time of 20.6 months, durvalumab was discontinued in 27% of all patients due to progressive disease. All patients with progressive disease were eligible for second-line treatment.

Immunotherapy for Stage III NSCLC: Durvalumab and Beyond

“…At the time of publication, a number of participants in this study were still receiving durvalumab, with a median follow-up of 20.6 months. 39 Taken together, these data support the PACIFIC data, but also identify that in real-world settings there are particular considerations, including tumor PDL1 expression, comorbidities, and autoimmune disease history, that may limit or curtail the use of durvalumab.…”

“…37 Separately, a prospective study of 26 patients with PDL1positive unresectable stage III NSCLC showed impressive efficacy for durvalumab consolidation treatment, with 12month PFS of 62% and 12-month OS of 100%. 39 This study differed in terms of including patients that had received concurrent or sequential chemoradiotherapy, and it included one patient with stage IV disease. At the time of publication, a number of participants in this study were still receiving durvalumab, with a median follow-up of 20.6 months.…”

Clinical Management and Outcome of Grade III Pneumonitis after Chemoradioimmunotherapy for Inoperable Stage III Non-Small Cell Lung Cancer—A Prospective Longitudinal Assessment

“…This was corroborated by the findings of the PACIFIC trial in which consolidation with the PD-L1 inhibitor durvalumab after CRT significantly prolonged PFS and OS in patients with inoperable stage III NSCLC [8][9][10]. Corresponding real-world studies confirmed the PACIFIC results and reported one-year PFS rates in the order of 50-65% [9,11,12]. In addition, combinations of CRT with different anti-PD-1 and anti-PD-L1 drugs are currently under evaluation [13][14][15][16].…”

“…Real-world studies from Shaverdian et al and Jung et al have reported on significant higher rates of symptomatic Grade II-III pneumonitis in the patients treated with concurrent CRT followed by durvalumab [9,25]. In another prospective study of 26 inoperable stage III NSCLC patients treated with durvalumab maintenance, an 18% rate of grade III pneumonitis was reported [11].…”

PD (L) 1-Inhibitors and Radiation: A Good Combination for Local and Systemic Effects?

“…Overall, a significant improvement in mPFS was achieved from 5.6 months to 16.6 months and the 4-year overall survival increased from 36.3% to 49.6% (Faivre-Finn et al, 2021). A series of so-called real world data analyses are able to confirm these positive effects of maintenance of durvalumab (Taugner et al, 2021). The positive effect of durvalumab is significantly greater, if time interval between the last irradiation and the first administration of durvalumab is not greater than 14 days, which underlines the positive interactions between RT and PD-(L) -1 inhibitors.…”