Adults with NSCLC and Impaired Performance Status Face Shorter Survival after ICI Treatment

Adults with advanced non-small cell lung cancer (NSCLC) and impaired performance status (PS) experience significantly shorter survival after treatment with immune checkpoint inhibitors (ICIs) and receive ICIs more often than those with better performance status, according to a study published in Cancer.

The researchers indicated that these findings align with prior retrospective evidence suggesting the need for the incorporation of adults with performance status ≥2 into randomized clinical trials.

“This collective evidence helps clarify that survival outcomes from pivotal phase III clinical trials of ICIs may not be generalizable to adults with impaired PS,” the authors wrote. “Therefore, caution should be used in counseling functionally impaired adults who are facing decisions about whether to pursue ICI treatment for advanced NSCLC.”

In this retrospective, single-site study cohort of 237 patients with advanced NSCLC who initiated ICI treatment from 2015 to 2017, researchers compared the overall survival (OS) of patients who had impaired PS (≥2) at the start of ICI treatment with those who had PS of 0 or 1. They then analyzed the association between ICI use in the last 30 days of life and the use of end-of-life care.

Overall, 35.4% of the study subjects had PS ≥2 and most patients (80.8%) received ICI as a second-line or later therapy. In patients with PS ≥2, the median OS was 4.5 months and 14.3 months for those with PS of 0 or 1 (HR, 2.5; P < 0.0001).

Of those who died (n = 184), 28.8% who had PS ≥2 received ICIs in their last 30 days of life compared with 10.8% of those who had PS of 0 or 1 (P = 0.002). Moreover, receipt of ICI in the last 30 days of life was correlated with decreased hospice referral (OR, 0.29; P = 0.008) and increased in-hospital deaths (OR, 6.8; P= 0.001), independent of PS.

It is currently unknown whether impaired PS is simply a poor prognostic marker or whether it can also predict an inability to mount an effective antitumor immune response to ICIs. However, several prospective, single-arm clinical trials are now ongoing to evaluate the activity of ICIs in adults with impaired PS. Though these studies will not fully address whether PS has predictive as well as prognostic value for ICIs, they will help better define the toxicity profiles of ICIs in patients with impaired PS. 

The authors indicated that tools should also be developed to “1) ascertain the goals and preferences of adults with NSCLC in the new cancer therapeutic landscape, which includes immunotherapy, to support shared decision making in appropriate clinical situations; and 2) educate candidates for ICI treatment and their caregivers about potential outcomes of treatment to help them prepare for the full range of possibilities.”

Notably, the standard of care for advanced NSCLC has changed since the time period evaluated within this study. Pembrolizumab (Keytruda) with or without chemotherapy is now a standard first-line therapy for patients with NSCLC whose tumors have PD-L1 expression ≥50%. Further, among adults with advanced NSCLC and PD-L1 expression <50%, pembrolizumab in combination with histology-based, platinum-doublet chemotherapy is now standard first line therapy. Given this, the researchers indicated that their findings underscore the need for future studies evaluating whether PS affects the activity of ICIs in the first-line setting. 

“A key feature of most prognostic models for adults with advanced cancer is PS,” the authors wrote. “Therefore, clinicians may find PS to be a useful guide in choosing patients with whom to have a careful discussion about the risks and benefits of ICI, including the possibility that ICI use could affect their [end-of-life] care and may increase the risk of in-hospital death.”

Reference:

Petrillo LA, El-Jawahri A, Nipp RD, et al. Performance Status and End-of-Life Care Among Adults With Non-Small Cell Lung Cancer Receiving Immune Checkpoint Inhibitors. Cancer. doi:10.1002/cncr.32782.