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

Patients with stage III non–small cell lung cancer and baseline grade 1 radiation pneumonitis post-chemotherapy could benefit from treatment with durvalumab.

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