Adjuvant Pembrolizumab May Improve Disease-Free Survival in Patients With Early-Stage NSCLC

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Adjuvant pembrolizumab may improve disease-free survival compared to placebo in patients with early-stage non–small cell lung cancer (NSCLC) following complete resection and adjuvant chemotherapy when indicated, investigators from the PEARLS/KEYNOTE-091 trial reported in a European Society for Medical Oncology (ESMO) Virtual Plenary session (Abstract VP3-2022).

The second interim analysis of the phase III study showed an increase in median disease-free survival from 42.0 months with placebo to 53.6 months with adjuvant pembrolizumab (hazard ratio [HR] = 0.76). Investigators also noted that the benefit was consistent across various levels of PD-L1 expression, including patients with a tumor proportion score of less than 1%.

“Overall, we believe that pembrolizumab has the potential to become a new adjuvant treatment option for patients with stage IB, stage II, and stage IIIA NSCLC following complete resection and adjuvant chemotherapy when recommended, regardless of PD-L1 expression,” said lead study author Luis Paz-Ares, MD, PhD, Professor of Medicine at Hospital Universitario 12 de Octubre, in Madrid.

Luis Paz-Ares, MD, PhD

Luis Paz-Ares, MD, PhD

As Dr. Paz-Ares reported, early-stage NSCLC accounts for up to 50% of all NSCLC diagnoses, and for patients with stage IB (with tumors at least 4 cm) to stage IIIA NSCLC, standard treatment involves resection followed by adjuvant platinum-based chemotherapy. However, the absolute 5-year overall survival benefit of adjuvant chemotherapy vs observation alone is only 5%, according to research published in The Lancet.

For the PEARLS/KEYNOTE-091 trial, investigators enrolled patients with confirmed stage IB, stage II, or IIIA NSCLC following complete surgical resection with negative margins (R0). Patients were required to provide tumor tissue for PD-L1 testing that was performed centrally using the 22C3 pharmDx assay. Adjuvant chemotherapy was not mandatory, but patients with stage IB disease were considered for that treatment, and adjuvant chemotherapy was strongly recommended for patients with stage II or III disease according to local or national guidelines. Chemotherapy was platinum-based and limited to four cycles or fewer.

Patients were randomly assigned to receive pembrolizumab at 200 mg every 3 weeks for up to 18 administrations (approximately 1 year) or placebo with the same scheduling. The study’s dual primary endpoints are disease-free survival in the global population and disease-free survival in patients with a PD-L1 tumor proportion score of at least 50%.

Improvement in Disease-Free Survival

Of the 1,177 patients randomly assigned to receive pembrolizumab or placebo, 380 completed treatment in the pembrolizumab arm and 381 completed treatment in the placebo arm. Pembrolizumab significantly improved the primary endpoint of disease-free survival in the overall population from 42 months in the placebo arm to 54 months in the pembrolizumab arm (HR = 0.76, P = .0014). The disease-free survival benefit of pembrolizumab was also observed across most of the prespecified subgroups.

“Pembrolizumab provided benefit regardless of pathological stage, PD-L1 expression, smoking status, or the presence of an EGFR mutation,” said Dr. Paz-Ares.

Overall survival data are still immature, but a nonsignificant trend was seen with pembrolizumab treatment. The 18-month rate of overall survival was 91.7% in the pembrolizumab arm vs 91.3% in the placebo arm (HR = 0.87, P = .17).

The safety profile observed with pembrolizumab was as expected and was manageable, said Dr. Paz-Ares. The incidence of grade 3 or greater adverse events and adverse events leading to discontinuation of therapy were higher in the pembrolizumab arm. Treatment-related deaths occurred in four patients receiving pembrolizumab.

Immune-mediated adverse events were also recorded more frequently with pembrolizumab, including a significant incidence of thyroid disorder, hyperthyroidism, pneumonitis, and skin rash.

Disease-free survival in the PD-L1-defined populations and overall survival will be tested at future analyses according to the analysis plan, said Dr. Paz-Ares.

Disclosure: Dr. Paz-Ares reported financial relationships with the following companies: Alkermes, Altum Sequencing, Daiichi Sankyo, Roche, MSD, Merck Serono, BMS, AstraZeneca, Lilly, Pfizer, PharmaMar, Bayer, Amgen, Janssen, GSK, Novartis, Ipsen, IO Biotech, Takeda, Sanofi, Tesaro, and Mirati. For full disclosures of the study authors, visit

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