FDA Approves Adjuvant Pembrolizumab for Stage IB-IIIA NSCLC


Results from the phase 3 PEARLS/KEYNOTE-091 trial have led to the FDA approval of adjuvant pembrolizumab for the treatment fully resected NSCLC.

The FDA has granted approval to adjuvant pembrolizumab (Keytruda) following resection and platinum-based chemotherapy for stage IB (T2a ≥4 cm), II, or IIIA non-small cell lung cancer (NSCLC).1

The approval is based on results from the phase 3 PEARLS/KEYNOTE-091 trial (NCT02504372), which showed adjuvant pembrolizumab to lead to improved disease-free survival (DFS) compared with placebo in patients with fully resected NSCLC.

KEYNOTE-091 is a global, randomized, phase 3 trial evaluating pembrolizumab vs placebo for the adjuvant treatment of patients with early-stage NSCLC after surgical resection, consisting of lobectomy or pneumonectomy, and with adjuvant chemotherapy when indicated.2

Investigators in the trial randomized 1177 patients in a 1:1 ratio to receive pembrolizumab (n = 590) or placebo (n = 587) intravenously at a dose of 200 mg every 3 weeks for up to 18 administrations. The median number of doses of pembrolizumab given to patients was 17 vs 18 for those who received placebo.

Enrollment in the trial was open to patients with an ECOG performance score of 0 or 1, and who were considered to have stage IB disease with a tumor of at least 4 cm, stage II, and stage IIIA disease.

The study had dual primary end points of DFS in the overall population regardless of PD-L1 expression and DFS in patients with a PD-L1 tumor proportion score (TPS) of greater than or equal to 50%. DFS in this trial is determined by whichever occurs first: time from randomization to the date of disease recurrence, occurrence of second primary lung cancer, occurrence of second malignancy, or death from any cause. Secondary end points of the trial included overall survival (OS), lung cancer-specific survival, and safety.

A presentation of the second interim analysis of the KEYNOTE-091 trial presented at the 2022 American Society of Clinical Oncology Annual Meeting, showed the median age of patients enrolled to be 65 years with almost 70% of patients being male. Over half of patients were from western Europe and all others were from eastern Europe, Asia, or other parts of the world. In the pembrolizumab arm, 35.6% patients had an ECOG score of 1, while 41.6% of patients receiving placebo did. Over 80% of patients between both treatment arms received adjuvant chemotherapy.2

A total of 55.8% of patients in the pembrolizumab group presented with stage II disease, 30.0% of patients had stage IIIA, and 14.2% had stage IB. In the placebo group, 57.6% of patients had stage II disease, 27.6% had stage IIIA, and 14.5% had stage IB. The overall majority of patients in both arms had a lobectomy (78.1% given pembrolizumab vs 79.0% given placebo).

In the second interim analysis of KEYNOTE-091, treatment with pembrolizumab resulted in a significant improvement in DFS for patients regardless of PD-L1 expression when compared with placebo. Patients who were given pembrolizumab had a median DFS of 58.7 months in the pembrolizumab arm (95% CI: 39.2, not reached) and 34.9 months in the placebo arm (95% CI: 28.6, not reached) (hazard ratio=0.73; 95% CI: 0.60, 0.89]).1

In terms of safety, the adverse event profile in KEYNOTE-091 was similar to that observed in other trials of pembrolizumab. AEs that were different from other trials included hypothyroidism (22%), hyperthyroidism (11%), and pneumonitis (7%). There were also 2 fatal adverse reactions of myocarditis.


1. FDA approves pembrolizumab as adjuvant treatment for non-small cell lung cancer. News release. FDA. February 26, 2022. Accessed February 26, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-adjuvant-treatment-non-small-cell-lung-cancer

2. O'Brien M, Paz-Ares L, Jha N, et al. EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 study of pembrolizumab versus placebo for completely resected early-stage non-small cell lung cancer (NSCLC): outcomes in subgroups related to surgery, disease burden, and adjuvant chemotherapy use. J Clin Oncol. 2022;40(suppl 16):8512. doi:10.1200/JCO.2022.40.16_suppl.8512

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