First-Line Durvalumab Improved Overall Survival Among Select Patients With Advanced Non-Small Cell Lung Cancer and ECOG Performance Status 2

While there were a high number of early fatal events seen with first-line durvalumab among patients with advanced, PD-L1 positive non-small cell lung cancer (NSCLC) and ECOG performance status 2 (PS2), when patients with grade ≥ 3 dyspnea were excluded and PS2 was confirmed independently by a second physician, there was a promising 6-month overall survival (OS) with an acceptable toxicity profile. 

“Monotherapy with an [immune checkpoint inhibitor] has now become the standard of care in [patients] with metastatic NSCLC with PD-L1 expression in ≥ 50% of tumor cells and with an ECOG PS of 0–1,” stated Michael Mark, MD, Kantonsspital Graubuenden, Chur, Switzerland, and coauthors. “An essential question in everyday clinical practice is whether these data can be extrapolated to [patients] with PS2.”

In the single-arm, multicenter phase 2 SAKK 19/17 trial, 48 patients with advanced PD-L1 positive NSCLC and PS2 received 1500 mg of durvalumab in 4 weekly doses. There was an unexpectedly high early number of fatal events due to tumor progression in the first 21 patients enrolled, which led to a protocol amendment. Patients with grade ≥ 3 dyspnea were excluded, and PS2 was required to be confirmed independently by a second physician. The primary end point was 6-month OS. Secondary end points included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), OS, safety, and quality of life. 

At a median follow-up of 23.3 months, the 6-month OS was 60%. ORR was 17%, DOR was 22.8 months, median PFS was 2.5 months, and median OS was 8.5 months. At that time, 33 patients had died due to progressive disease (70%), infection (12%), heart failure (9%), respiratory insufficiency (3%), stroke (3%) and colonic perforation (2%). After patients with grade ≥ 3 dyspnea were excluded, 3 additional early fatal events occurred. Grade ≥ 3 adverse events occurred in 81% of patients and included lung infection (19%), dyspnea (15%), hypertension (10%), and respiratory failure (10%). Grade ≥ 3 treatment-related adverse events were reported in 19% of patients and included colitis (8%), increased lipase (6%), hepatitis (4%), and colonic perforation (2%).

“First-line durvalumab in PS2 patients with advanced PD-L1 positive NSCLC results in a high number of early fatal events [however] when patients with grade ≥ 3 dyspnea are excluded a promising 6-month OS with an acceptable toxicity profile can be observed,” concluded Dr Mark et al. “Durvalumab could be an option instead of single agent chemotherapy for PS2 patients who are not candidates for platinum doublet chemotherapy provided they are well selected.” 

Source: 

Mark M, Froesch P, Gysel K, et al. First-line durvalumab in patients with PD-L1 positive, advanced non-small cell lung cancer (NSCLC) with a performance status of 2 (PS2). Primary analysis of the multicenter, single-arm phase II trial SAKK 19/17. Eur J Cancer. Published online: February 5, 2024. doi:10.1016/j.ejca.2024.113600