Despite Frequent Immune Checkpoint Inhibitor Use, Patients with Advanced NSCLC Face Shorter Survival

Patients with advanced non-small cell lung cancer (NSCLC) who are limited in their daily functions are often treated with immune checkpoint inhibitors. However, research findings show this does not help extend survival for this population.

A study published in Cancer evaluated 237 adults, ranging in age from 37 to 91, with advanced NSCLC who were mostly white, smoked 10 years or more and had a KRAS gene mutation. All patients in the study began immune checkpoint inhibitor treatment from 2015 to 2017 — 80.8% of patients received this as second-line or later therapy.

Immune checkpoint inhibitors are drugs that block proteins called checkpoints that are made by some types of immune system cells, such as T cells, and when they are blocked, T cells can try to kill cancer cells.

In examining performance status, 35.4% of patients had a score of 2 or greater, meaning patients were capable of self-care but not able to work, capable of limited self-care or completely disabled.

Compared with patients who had a better performance score — zero or 1, meaning they were fully active or able to do light housework — who had an overall survival rate of 14.3 months, patients with a score of 2 or greater saw a median overall survival of 4.5 months.

The researchers also learned that among the 184 patients who died, 28.8% who had a score of 2 or greater received immune checkpoint inhibitors in the last month of life compared with 10.8% of patients with a score of zero or 1.

“Our findings also demonstrate an increased frequency of immune checkpoint inhibitor initiation and continuation near the end of life among adults with advanced NSCLC and impaired performance score,” the researchers wrote. “In addition, the use of immune checkpoint inhibitors near the end of life in the overall cohort was associated with increased health care utilization, namely, increased hospitalization and in-hospital death, decreased referral to hospice and shorter hospice length of stay, regardless of performance score.”

The findings of the study highlight a need for the inclusion of adults with a poorer performance score into clinical trials, according to the researchers. In addition, they called for tools to be developed, such as supporting shared decision making in appropriate clinical situations for adults with NSCLC and educating patients eligible for immune checkpoint inhibitor treatment and their caregivers about potential outcomes of the therapy and prepare them for potential tradeoffs.

“The mechanism of the relation between immune checkpoint inhibitor use close to death and higher intensity end of life health care utilization warrants further study,” the researchers wrote. “The forced tradeoff between payment for potentially life-extending therapy and comfort-focused care in hospice likely contributes to this trend. However, it is also possible that increased hospitalization of adults with impaired performance score who receive immune checkpoint inhibitors close to the end of life reflects increased admission for disease progression or suspected toxicity in this frail population, a question that warrants further investigation.”