Use of ICI Therapy Beyond 2 Years Yields No Outcome Benefit in NSCLC

Non–small cell lung cancer clinical highlights

There was no difference in overall survival (OS) in patients with non–small cell lung cancer (NSCLC) who were administered fixed-duration immune checkpoint inhibitor (ICI) treatment for 2 years vs patients who received ICI treatment indefinitely, according to results of a retrospective study published in JAMA Oncology.¹

After a median follow-up of 14.0 months (range, 0.1-50.9), overall survival was 79% (95% CI, 66%-87%) in the fixed-duration group vs 81% (95% CI, 77%-85%) in the indefinite-duration group. In the fixed- duration group, the hazard ratio for death was 1.26 (95% CI, 0.77-2.08) after unadjusted analysis and 1.33 (95% CI, 0.78-2.25) in the indefinite-duration group. On adjusted analysis, investigators also reported no difference between the patient groups.

In addition, secondary analysis revealed that 11 patients in the fixed-duration cohort subsequently progressed; these patients were rechallenged with ICI after 30 days without treatment. Eight patients received ICI monotherapy and 3 patients received ICI plus chemotherapy. In this rechallenge, the median time from cessation of frontline treatment to the initiation of second-line treatment was 7.4 months (range, 1.8-26.9). After the ICI rechallenge, time from randomization to objective tumor progression on next-line treatment or death was 8.1 months.

Electronic health records in the Flatiron Health database of 14,406 patients from 280 cancer clinics in the US who started frontline ICI therapy for NSCLC were reviewed 760 days after initiation of therapy.

In 1091 patients who continued treatment at 2 years after exclusion criteria were applied, 113 patients were included in the fixed-duration group and 593 patients were identified as the indefinite-duration group. A total of 13,315 patients had discontinued treatment prior to 2 years.

In the fixed-duration group, the median age was 69 years, 54.9% were female, and 76.1% were White. In the indefinite-duration group, the median age was 69 years, 47.6% were female, and 69.8% were White. More patients in the fixed-duration group vs the indefinite-duration group were likely to have a history of smoking, 99% vs 93%, respectively (P = .01), and were treated at an academic center, 22% vs 11%, respectively (P = .001).

The use of ICI monotherapy was more common in the fixed-duration group vs the indefinite-duration group, 52% vs 46%, respectively (P = .39), and PD-L1 status distribution was similar for both groups. In the fixed-duration group, ECOG performance status of 0, 1, and 2 or greater was 30%, 49.6%, and 12.4%, respectively. In the indefinite-duration treatment group, ECOG performance status of 0, 1, and 2 or greater was 34.4%, 42.8%, and 13.3%, respectively.

Although the use of ICI therapy in NSCLC has had a significant impact on outcomes, the duration of ICI for optimal benefit remains unclear. The researchers noted that key pivotal studies have evaluated the use of frontline immunotherapy for up to 2 years, but in clinical practice, many patients continue therapy beyond that time point. In particular, in KEYNOTE-010 (NCT01905657) and KEYNOTE-024 (NCT02142738), patient survival was 83% and 82%, respectively, 3 years after completing 2 years on pembrolizumab (Keytruda).

Key implications of these findings support treatment discontinuation at 2 years, which is similar to prior studies.^2,3 Another implication suggests that patients who received fixed-duration therapy may benefit from rechallenge with ICI, despite progression after ICI treatment is halted. Although this particular finding was identified in a small subcohort, the promising results may lead to further clinical trials.

REFERENCES

1. Sun L, Bleiberg B, Hwang WT, et al. Association Between Duration of Immunotherapy and Overall Survival in Advanced Non-Small Cell Lung Cancer. JAMA Oncol. 2023;e231891. doi:10.1001/jamaoncol.2023.1891

2. Reck M, Rodrigeuz-Abreu D, Robinson AG, et al. Five-year outcomes with pembrolizumab versus chemotherapy for metastatic non–small-cell lung cancer with pd-l1 tumor proportion score ≥ 50%. J Clin Oncol. 2021;39(21):2239-2349. doi: 10.1200/JCO.21.00174

3. Herbst RS, Garon EB, Kim D-W, et al. Long-term outcomes and retreatment among patients with previously treated, programmed death-ligand 1‒positive, advanced non‒smallcell lung cancer in the KEYNOTE-010 Study. J Clin Oncol; 2020;38(14):1580-1590. doi:10.1200/JCO.19.02446