Durvalumab Appears to be Safe and Efficacious in Stage III NSCLC With Baseline Radiation Pneumonitis

Durvalumab (Imfinzi) may prove to be safe and effective for patients with stage III non–small cell lung cancer with grade 1 baseline radiation pneumonitis after chemoradiotherapy, according to a study published in Lung Cancer.

The median follow-up was 16.1 months, with a median of 13 lines of treatment with durvalumab. The median progression-free survival (PFS) was 11.4 months (95% CI, 7.1–not reached) and the median overall survival (OS) was not reached. Of 35 patients, investigators observed PFS events in 57% and OS events in 20%.

Patients included in the study underwent concurrent chemoradiotherapy, 25% of whom developed baseline grade 1 radiation pneumonitis and 35 being enrolled in the study. Patients had a median age of 69 years, 54% had stage IIIA disease, and 72% had an ECOG performance status of 1. Chronic obstructive pulmonary disease (COPD) was identified in 31% of patients, none had pre-existing interstitial lung disease besides radiation pneumonitis prior to the start of durvalumab.

Discontinuation of durvalumab occurred in 21 patients within 1 year from the start of treatment. Reasons for discontinuation included progressive disease (40%), adverse effects (AEs; 14%), and other reasons (6%).

Grade 3 or higher AEs occurred in 26% of patients, 3% of whom had grade 5 events. Treatment-related AEs (TRAEs) of grade 3 or higher occurred in 14% of patients and included pneumonitis or radiation pneumonitis, malaise, immune-related meningitis, platelet count reduction, and rash. Additionally, 2 patients who developed platelet count reduction, and rash.

Potentially treatment-related pneumonitis resulted in 1 death. Discontinuation of durvalumab during the follow-up period was necessary in 11% of patients because of TRAEs such as pneumonitis or radiation pneumonitis (n = 2), malaise (n = 1), and meningitis (n = 1).

Grade 2 or higher pneumonitis or radiation pneumonitis was observed in 31% of patients, with 28% developing grade 2 and 3% developing grade 5. The median time was 2.8 months from initiation of durvalumab to the onset of pneumonitis. Grade 2 or higher pneumonitis or radiation pneumonitis cases occurred in 55% of patients within 3 months. Grade 2 exacerbation of radiation pneumonitis was reported in 7 patients, 3 had grade 2 immune-related pneumonitis, and 1 had grade 5 immune-related pneumonitis.

Grade 5 pneumonitis developed in a 75-year-old man who had COPD. The patient had previously smoked 1 pack a day for 30 years. He was given chemotherapy and concurrent intensity-modulated radiotherapy at 2 Gy for 30 fractions. After 2.3 months of starting durvalumab, grade 3 immune-related pneumonitis occurred. After pneumonitis was diagnosed, he was given 30 mg per day of prednisone and was then reduced to 20 mg per day at 4.2 months. Re-exacerbation of pneumonitis occurred, and he died 3 days later.

Of the 10 patients with grade 2 pneumonitis or radiation pneumonitis, 8 improved with corticosteroid therapy and durvalumab withdrawal, while 2 improved with durvalumab withdrawal alone.

Reference

Sugimoto T, Fujimoto D, Sato Y, et al. Prospective multicenter cohort study of durvalumab for patients with unresectable stage III non-small cell lung cancer and grade 1 radiation pneumonitis. Lung Cancer. Published online July 13, 2022. doi:10.1016/j.lungcan.2022.07.005