Real-world survey of pneumonitis/radiation pneumonitis among patients with locally advanced non-small cell lung cancer treated with chemoradiotherapy after durvalumab approval: A multicenter retrospective cohort study (HOPE-005/CRIMSON).

Abstract

9039 Background: Durvalumab was approved as a consolidation therapy after chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (NSCLC) and established as the standard of care. However, since the approval of durvalumab, little has been reported on the frequency, severity, or clinical course of pneumonitis/radiation pneumonitis throughout the course of CRT. Methods: We conducted a 17-center, retrospective cohort study of consecutive patients with locally advanced NSCLC who received concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy between May 2018 and May 2019. Results: A total of 275 patients were included; their median age was 69.9 (range, 40.3-87.5), mean V20 was 19.4% (range, 1.4-37.9), and mean "mean lung dose" was 10.9 Gy (range, 1.5-31.3). Of these, 204 patients received durvalumab consolidation therapy (74.2%). Median follow-up time from the initiation of CCRT was 8.4 months (range, 1.5-15.7). During follow-up, 225 patients (81.8%) developed any-grade pneumonitis/radiation pneumonitis. Of these, more than half (134 of 225) were asymptomatic (grade 1), 18 (6.5%) were ≥grade 3, and 4 patients (1.5%) had fatal pneumonitis/radiation pneumonitis. By the time of initial assessment of response to CCRT, 64 (23.3%) patients had developed radiation pneumonitis. Logistic regression revealed that only V20 ≥25 % was an independent risk factor of symptomatic (≥grade 2) pneumonitis/radiation pneumonitis (OR: 2.74, 95% CI: 1.35-5.53, p = 0.0045). Of the 275 patients, 67 were treated with corticosteroids for pneumonitis/radiation pneumonitis (24.7%), and 14 (5.1%) needed home oxygen therapy after the treatment of pneumonitis/radiation pneumonitis. Among patients treated with corticosteroids, 21 patients received durvalumab rechallenge. Of the 21 patients, 6 (29%) showed pneumonitis/radiation pneumonitis relapse, of which 3 (14%) resulted in suspension of durvalumab rechallenge, but none were fatal. Conclusions: Although over four-fifths of the patients treated with CCRT after the approval of durvalumab developed pneumonitis/radiation pneumonitis, more than half of them were asymptomatic, and ≥grade 3 events accounted for 6.5%. Sometimes patients needed corticosteroid therapy, which was in many occasions effective, and some also underwent durvalumab rechallenge. V20 was an independent risk factor of symptomatic pneumonitis/radiation pneumonitis.

Attitudes and Practices of Immune Checkpoint Inhibitors in Chinese Patients With Cancer: A National Cross-Sectional Survey

“…Suresh et al indicated that the rate of ICI-induced pneumonitis in lung cancer patients could be as high as 7–19% ( Suresh et al, 2018 ). A study reported a rate of 33% of pneumonitis with any symptoms (grade ≥2) ( Saito et al, 2020 ). A meta-analysis showed that the pooled rates of grades 2, 3, 4, and 5 pneumonitis were 17.8, 7.9, and 14%, respectively ( Dawe et al, 2016 ).…”

Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC: A post-hoc analysis of the PACIFIC trial

“…pneumonitis/RT-pneumonitis with the PACIFIC regimen [31]. Thyroid disorders, including hypothyroidism (8.8%) and hyperthyroidism (2.5%), were the most common non-pneumonitis imAEs in PACIFIC, with a total incidence of 11.4% among patients who received durvalumab.…”

A Canadian Perspective on the Challenges for Delivery of Curative-Intent Therapy in Stage III Unresectable Non-Small Cell Lung Cancer

“…In the PACIFIC trial, any grade pneumonitis occurred at a rate of 33.9% in patients receiving durvalumab, with grade ≥ 3 pneumonitis occurring in 3.4% (24.8 and 2.6% in the placebo arm, respectively) [10]. Real-world data have reported frequencies of any grade and grade ≥ 3 pneumonitis of 20-80% and approximately 6%, respectively, with some studies reporting pneumonitis as a negative prognostic factor for survival [18,57,59,60]. Pneumonitis is a particularly concerning immune-related adverse event in patients with stage III lung cancer, as prior radiotherapy may act synergistically to increase its risk of occurrence [61].…”

“…Re-challenge with durvalumab can be considered after resolution of symptoms; however, guidelines on safely re-challenging are limited [60]. In two small retrospective studies, re-challenge with durvalumab was shown to be feasible, leading to pneumonitis recurrence in 14 and 29% of patients [59,60]. To optimize patient outcomes, the decision of durvalumab re-challenge should be made with an MDT.…”