The positive results observed with immune checkpoint inhibitors (ICIs) in clinical trials may not translate to patients with advanced cancers who are ineligible for such trials, according to a study published in JAMA Oncology.

The study showed no overall survival difference between ICI therapy and non-ICI therapy in patients who were ineligible for clinical trials due to poor performance status or organ dysfunction.

This retrospective study included 34,131 patients with recurrent or newly diagnosed metastatic cancer. Patients had non-small cell lung cancer, urothelial cell carcinoma, renal cell carcinoma, or hepatocellular carcinoma. The patients’ median age was 70 years (range, 62-77 years), 42% were women, and 69% were White.

There were 9318 patients (27.3%) who were ineligible for clinical trials. This included 6570 patients (71%) who had a performance status score of 2 or higher and 3416 (37%) who had organ dysfunction.

Of the trial-ineligible group, 1967 patients received ICI monotherapy, 805 received ICI combination therapy, and 6547 received non-ICI therapy.

The restricted mean survival times (RMSTs) were similar across the treatment groups at 12 months and 36 months.

At 12 months, the RMST was 7.8 months in the ICI monotherapy group, 7.8 months in the ICI combination group, and 8.1 months in the non-ICI group. At 36 months, the RMST was 15.0 months, 13.9 months, and 14.4 months, respectively.

The median overall survival was 9.72 months in the ICI monotherapy group, 9.33 months in the ICI combination group, and 8.75 months in the non-ICI group.

In the first 6 months after starting treatment, there was a higher risk of death with ICI monotherapy (adjusted hazard ratio [aHR], 1.19; 95% CI, 1.11-1.27) and ICI combination therapy (aHR, 1.14; 95% CI, 1.08-1.22), compared with non-ICI therapy.

However, at 6 months after treatment initiation and beyond, the risk of death was lower for ICI monotherapy (aHR, 0.80; 95% CI, 0.74-0.84) and similar for ICI combination therapy (aHR, 1.0; 95% CI, 0.89-1.13) and non-ICI therapy.

“Collectively, these results suggest that phase 3 trials that show a survival benefit for ICI therapy may not generalize to patients with poor PS [performance status] or organ dysfunction; future prospective trials are needed to confirm these findings,” the researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Parikh RB, Min EJ, Wileyto EP, et al. Uptake and survival outcomes following immune checkpoint inhibitor therapy among trial-ineligible patients with advanced solid cancers. JAMA Oncol. Published online November 4, 2021. doi:10.1001/jamaoncol.2021.4971