New 5-Year KEYNOTE-024 Data Show Pembrolizumab Continues to Prolong OS in NSCLC

Patients with non–small cell lung cancer and PD-L1 tumor proportion scores of at least 50% had a median 5-year overall survival rate of 26.3%, showing a significant improvement versus standard of care.

New 5-year data from the closely watched KEYNOTE-024 trial (NCT02142738) show pembrolizumab (Keytruda) roughly doubles 5-year overall survival (OS) rates, from 16.3% to 31.9%, versus chemotherapy in patients with metastatic non–small cell lung cancer (NSCLC) with PD-L1 tumor proportion scores (TPS) above 50%.

The findings add new evidence to the case for the PD-1–targeting monoclonal antibodies in the first-line setting for metastatic NSCLC. The report was published in Journal of Clinical Oncology.1

KEYNOTE-024 is a randomized, open-label, phase 3 trial comparing first-line pembrolizumab monotherapy with platinum-based chemotherapy in patients with high PD-L1 expression. Earlier results from the study showed the immunotherapy led to improved progression-free survival (PFS) and OS.

Corresponding author Martin Reck, MD, PhD, of the German Center for Lung Research, and colleagues, wrote that the new 5-year survival data are particularly important in this case because such data are difficult to achieve due to relatively low survival rates in this population.

The investigators also noted earlier results from the single-arm, phase 1b KEYNOTE-001 study (NCT01295827) showing that patients with NSCLC and PD-L1 TPS scores of at least 50% who underwent pembrolizumab monotherapy had a 5-year OS rate of 29.6% (95% CI, 7.7%-56.1%).2

The new study involved 305 patients, who were randomly assigned to either pembrolizumab at 200 mg dose every 3 weeks for up to 35 cycles (n = 154) or platinum-based chemotherapy (n = 151). The primary end point was PFS, with OS as the secondary end point.

The median time from randomization to data cut-off was 59.9 months, and the final data cutoff was June 1, 2020. Patients in the pembrolizumab group received treatment for a median of 7.9 months and those in the chemotherapy group received treatment for a median of 3.5 months.

Patients whose disease progressed with chemotherapy were allowed to cross over to immunotherapy, with 99 patients ultimately switching therapy. Of those, 83 crossed over to pembrolizumab on-study, and the remaining 16 switched to anti–PD-1/L1 therapy outside of the trial.

Just over half of the patients in the pembrolizumab group (52.9%) received additional therapy for their disease, including 12 patients who received a second course of pembrolizumab.

The study found that by data cutoff, most patients had either progressed per investigator assessment or died, at 81.8% of the pembrolizumab group and 93.4% of the chemotherapy group. For those taking pembrolizumab, median PFS was 7.7 months (95% CI, 6.1 to 10.2 months). In the chemotherapy group, median PFS was 5.5 months (95% CI, 4.1 to 6.2 months).

Median OS, however, was 26.3 months in the pembrolizumab group (95% CI, 18.3-40.4 months) compared with just 13.4 months (9.4-18.3 months) in the chemotherapy group (HR, 0.62; 95% CI, 0.48-0.81). Among the 39 patients who received the full 35 cycles of pembrolizumab, 82.1% were still alive at 5 years. The investigators also found that toxicity did not improve with longer treatment exposure.

Reck and colleagues wrote that the findings are significant, and particularly impressive, given the high crossover rate from the chemotherapy group to subsequent anti–PD-1/L1 therapy.

“This high effective crossover rate may have reduced the observed treatment effect for pembrolizumab versus chemotherapy given that immunotherapy agents (including pembrolizumab) have demonstrated improved OS over chemotherapy in the second-line or later setting,” they wrote.

Reck and colleagues said that these new data, paired with other data from the KEYNOTE studies, paint a clear picture of pembrolizumab’s efficacy as a first-line therapy in this patient group and in other NSCLC patient populations. The investigators said epidemiological data are already driving down lung cancer mortality rates in the United States.

“Five-year outcomes in KEYNOTE-024 suggest that availability of immunotherapy may result in further improvement in lung cancer survival at the population level and that pembrolizumab may be transforming metastatic NSCLC into a treatable chronic disease for patients who meet eligibility criteria,” they concluded.

References

1. Reck M, Rodríguez-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. Published online ahead of print April 19, 2021. doi:10.1200/JCO.21.00174

2. Garon EB, Hellmann MD, Rizvi NA, et al. Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study. J Clin Oncol. 2019;37(28):2518-2527. doi:10.1200/JCO.19.00934