Durvalumab Timing Might Affect Pneumonitis Risk Following Chemoradiotherapy in NSCLC

Patients with locally advanced non–small cell lung cancer (NSCLC) who receive Imfinzi (durvalumab) within 2 weeks of their last day of thoracic radiotherapy may be at a higher risk of developing pneumonitis, according to a new study.

The authors of the study, published in Asia-Pacific Journal of Clinical Oncology, said the findings show the importance of careful monitoring in patients who receive durvalumab soon after radiation. They explained that the anti–programmed death ligand 1 (PD-L1) inhibitor durvalumab has become the standard of care in patients with unresectable locally advanced NSCLC who had stable disease and no symptomatic pneumonitis following chemoradiotherapy.

Yet, they also noted that despite a safety profile comparable to other types of immunotherapy, durvalumab clinical trial data suggest that Japanese patients were at a significantly higher risk of pneumonitis than the general study population (73.6% vs 33.9%). Several risk factors for interstitial lung disease following immune checkpoint inhibitor therapy have been identified in patients of Asian heritage, including tumor histology, smoking status, preexisting disease, and a history of asthma or chronic obstructive pulmonary disease. In addition, the authors said, intensity-modulated radiation therapy has been shown to reduce the risk of grade 3 or above radiation pneumonitis.

However, to date no one has examined whether the timing of durvalumab administration might impact the risk of pneumonitis, the investigators said. They decided to study a case series of 26 consecutive patients who received durvalumab following chemoradiotherapy to see whether they could identify risk factors for pneumonitis. Most of the patients (62%) experienced grade 1 pneumonitis, and 27% and 12% developed grade 2 and 3 pneumonitis, respectively. None of the patients developed grade 4 pneumonitis.

Overall, the patients had a median progression-free survival (PFS) of 15.6 months (95% CI, 8.7 months-not available), although patients with a PD-L1 expression level of less than 50% had a median PFS of just 6.4 months. PFS was not reached in the cohort of patients with greater than 50% PD-L1 expression.

When investigators examined durvalumab timing and pneumonitis outcomes, they found that the 6 patients whose durvalumab therapy began within 14 days of their final radiotherapy treatment had a significantly higher risk of developing grade 2 or above pneumonitis compared with those receiving durvalumab more than 2 weeks after radiotherapy (HR, 0.19; 95% CI: 0.06-0.59).

The authors said the data suggest that earlier durvalumab administration might increase the risk of serious pneumonitis, because the medication could masks the early signs of pneumonitis, thus increasing the risk that the complication becomes severe. At the same time, the authors noted that earlier research suggests overall survival may improve when patients are given durvalumab within 14 days of radiation therapy.

They said the decision about when to start durvalumab should therefore be made cautiously and physicians should carefully monitor patients for signs of pneumonitis for at least 2 months following radiation.

The authors cited several limitations to their research, including its small sample size, its retrospective nature, and differences in the patient populations and characteristics between this study and clinical trials for durvalumab.

Reference

Harada D, Shimonishi A, Saeki K, et al. Early administration of durvalumab after chemoradiotherapy increased risk of pneumonitis in patients with locally advanced non-small cell lung cancer. Asia Pac J Clin Oncol. Published online June 10, 2022. doi:10.1111/ajco.13803