Osimertinib-related pneumonitis incidence higher in real-world lung cancer population
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Drug-related pneumonitis occurred among 18% of patients receiving osimertinib for advanced epidermal growth factor receptor mutation-positive non-small cell lung cancer, according to study results published in CHEST.
“Drug-related pneumonitis (DRP) associated with first-line osimertinib treatment occurred at a higher rate in the real-world population than in previous study cohorts,” Yuki Sato, MD, of the department of respiratory medicine at Kobe City Medical General Hospital, and colleagues wrote. “[Additionally,] half of the patients demonstrated transient asymptomatic pulmonary opacity (TAPO) features, and TAPO did not negatively impact prognosis.”
In a retrospective multicenter cohort study, Sato and colleagues analyzed 452 (median age, 72 years; 67.3% women) Japanese patients with advanced epidermal growth factor receptor mutation-positive non-small cell lung cancer (NSCLC) assigned osimertinib (Tagrisso, AstraZeneca) as a first-line treatment between August 2018 and December 2019, with chest CT scans and clinical information gathered until June 2020.
DRP incidence served as the study’s primary endpoint.
Of the total cohort, researchers found that 80 (18%) patients had any-grade DRP, including 21 (4.6%) of grade 3 or higher and five patients with grade 5 DRP.
Radiologic features of DRP on CT scans included organizing pneumonia (38%), simple pulmonary eosinophilia (26%), hypersensitivity pneumonia (23%), diffuse alveolar damage (11%) and nonspecific interstitial pneumonia (3%).
Although there was no overall survival (OS) difference between those with vs. without DRP, those with DRP had a significantly shorter progression-free survival (PFS; 11.3 months vs. 20.7 months; P < .001) and a longer time to treatment failure (5.6 months vs. not reached; P < .001) compared with those without DRP.
Along with a DRP diagnosis, 37 (46%) patients also had TAPO. Although DRP was linked to poor treatment efficacy in 3-month landmark analysis, researchers found that TAPO was linked to better efficacy. For those with TAPO, PFS was not reached in the study, whereas it was 6.5 months for those without TAPO and 20.7 months for those without DRP. OS was not reached in all the groups.
Additionally, researchers observed smoking history (HR = 1.72; 95% CI, 1.01-2.89) was an independent risk factor for DRP on multivariable analysis. Although 24% of patients with nonfibrotic interstitial lung abnormalities (ILAs) and 43% with fibrotic ILA had DRP, it was not observed as an independent risk factor.
“In previous reports, DRP incidence in the Japanese population consistently was higher than that in global studies,” Sato and colleagues wrote.
(18% for all grades and 4.6% for grade 3 or more) exceed the numbers for the FLAURA Japanese subsets, we propose that clinicians should pay special attention to DRP in real-world settings.”
This study by Sato and colleagues adds to the literature knowledge of how to approach DRP risk assessment, monitoring and intervention, according to an accompanying editorial by Jennifer D. Possick, MD, of the section of pulmonary, critical care and sleep medicine at Yale University School of Medicine.
“Precision management of patients with NSCLC should not end with the initiation of a treatment plan,” Possick wrote. “Continued exploration of DRP in real-world populations provides a solid foundation for nuanced decision-making, both at initiation of therapy and as complications arise.”
Ideally, a personalized therapeutic plan would include an individualized risk assessment and plan for mitigation and monitoring, Possick added.
"Real-world studies such as this illuminate patient risk factors that merit caution and DRP features that should be monitored or managed more (or less) aggressively, adding crucial perspective to our experience with targeted therapies and defining future questions,” she wrote.