Abstract
Background: Consolidation durvalumab improved overall survival (OS) in locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy (CRT) in the PACIFIC trial; however, pneumonitis was increased with durvalumab. We sought to examine real-world outcomes with the PACIFIC paradigm, especially factors associated with pneumonitis, using a multi-institutional review. Methods: Patients with LA-NSCLC treated with CRT followed by durvalumab from January 2017-February 2019 were identified at 2 institutions. We characterized demographics, tumor factors, radiotherapy, and duration of durvalumab. We examined pneumonitis outcomes including re-challenge success, with secondary endpoints of progression-free survival (PFS) and OS. Results: Thirty-four patients were included with median follow-up of 12 months (range, 3 to 20 months); 94% had stage III disease. The cumulative grade >2 pneumonitis rate was 26.5% with 2 patients developing grade 3 pneumonitis and no grade 4/5 events. Median time to pneumonitis after RT was 2.4 months (range, 0 to 4.9 months). Pneumonitis management included median prednisone dose of 60 mg for median taper of 6 weeks with durvalumab held for median of 4.5 weeks (range, 2 to 8 weeks); 70% of pneumonitis patients received durvalumab re-challenge, with pneumonitis recurring in 14% of patients. 3-month and 6-month pneumonitis-free-survival were 76.9% and 73.6%, respectively; 9- and 12-month OS were 96% (75.1-99.8%), 86.6% (63.5-95.5%), respectively; 9- and 12-month PFS were 68% (47.5-82.5%), 48.7% (25.3-68.3%). Pneumonitis development did not significantly impact PFS or OS (P>0.05). Conclusions: Among LA-NSCLC patients treated with CRT followed by consolidation durvalumab, more than 25% developed symptomatic pneumonitis. In this small case series, pneumonitis did not appear to negatively impact survival, and durvalumab re-challenge appeared feasible after pneumonitis treatment with steroids.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 6690-6700 |
| Number of pages | 11 |
| Journal | Journal of Thoracic Disease |
| Volume | 12 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2020 |
Funding
ICMJE uniform disclosure form (available at http:// dx.doi.org/10.21037/jtd-20-1792). Dr. SW reports grants from 1 UM1 CA186704-01, other from F. Hoffmann-La Roche Ltd, other from Ariad, other from Pfizer Pharmaceuticals, Inc., other from Hengrui Therapeutics, other from Xcovery, other from EMD Serono Research & Development Institute, Inc., other from Checkpoint Therapeutics, Inc., other from Genentech, Inc., other from Lilly, other from Stemcentrx, Inc., other from Ignyta, Inc., other from Bristol-Myers Squibb Pharmaceutical, other from Synermore Biologics Co., Ltd., other from Novartis Pharmaceuticals Corporation, other from Merck & Company, Inc., other from NewLink Genetics Corporation, other from Celegene, outside the submitted work. Dr. NM reports personal fees from Astra Zeneca, personal fees from Bristol Meyers Squibb, personal fees from Abbvie, personal fees from Genentech, outside the submitted work. Dr. JB reports personal fees from AstraZeneca, outside the submitted work. Dr. TJK reports personal fees from AstraZeneca, personal fees from AstraZeneca, personal fees from Varian Medical Systems, personal fees from Abbvie Inc, outside the submitted work. Dr. MR reports personal fees and non-financial support from ViewRay, non-financial support from Varian, outside the submitted work. Dr. CR reports grants and personal fees from Varian, grants from Elekta, other from Radialogica, outside the submitted work. The other authors have no conflicts of interest to declare. Funding: This work was supported by Clinical and Translational Science Award (CTSA) Grant (UL1 TR000448) and Siteman Comprehensive Cancer Center and NCI Cancer Center Support Grant P30 (CA091842).
Keywords
- Chemoradiotherapy (CRT)
- Durvalumab
- Immune-related adverse events (irAE)
- Non-small cell lung cancer (NSCLC)
- Pneumonitis
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
