Adjuvant Pembrolizumab Yields Impressive Disease-Free Survival Outcomes in Select Patients With NSCLC


Pembrolizumab was associated with the first positive clinical trial outcomes in the adjuvant setting of non–small-cell lung cancer.

Mary O’Brien, MD, FRCP

Mary O’Brien, MD, FRCP

Pembrolizumab significantly extended disease-free survival among patients with stage IB to IIIA non–small-cell lung cancer (NSCLC) in the adjuvant setting following surgical resection, according to an interim analysis of the phase 3 KEYNOTE-091 trial (also known as EORTC-1416-LCG/ETOP-8-15 – PEARLS [NCT02504372]).1 Notably, the observed significant improvement in comparison with placebo, which met the trial’s primary end point, was seen across participants regardless of PD-L1 expression.

Interim findings demonstrated that patients whose tumors did express PD-L1 with a tumor proportion score (TPS) of 50% or higher experienced improved DFS following pembrolizumab treatment, however, there was not enough statistically significant linked to this dual primary end point in accordance with the prespecified statistical plan. Researchers will continue to assess DFS in patients whose tumors harbor high levels of PD-L1 and assess overall survival (OS) as a key secondary end point.

Pembrolizumab is an anti–programmed death receptor-1 (PD-1) therapy which functions by blocking the interaction between PD-1 and its ligands PD-L1 and PD-L2, thus activating T lymphocytes and increasing the body’s immune system to help detect and fight tumor cells. KEYNOTE-091 represents the first positive trial to assess this agent in the adjuvant setting of NSCLC, which is known to be the most common form of lung cancer, and which accounts for 85% of lung cancer cases.

“Surgery is widely considered the first and most important intervention for most patients with early-stage non-small cell lung cancer; however, an estimated 43% of those who undergo surgery will see their disease return,” co-principal investigator Mary O’Brien, MD, FRCP, The Royal Marsden, NHS Foundation Trust, and professor at Imperial College, London, UK, said in a news release. “Data from KEYNOTE-091 suggest adjuvant [pembrolizumab] reduced the risk of disease recurrence or death after surgery in the overall population of patients with stage IB to IIIA non–small cell lung cancer.”

KEYNOTE-091 enrolled 1177 patients who were randomized 1:1 to receive either 200 mg of pembrolizumab every 3 weeks for 1 year (maximum 18 doses) or placebo every 3 weeks for 1 year (maximum 18 doses). Eligible participants included patients with stage IB to IIA NSCLC who had received prior surgical resection (either lobectomy or pneumonectomy). DFS was calculated as the time between randomization and the date of either disease recurrence, occurrence of second lung cancer primary, occurrence of second primary, or death from any cause, whichever occurred first.

Pembrolizumab’s safety profile was found to be consistent with previously reported data. However, full results are expected to be represented at an upcoming medical meeting, as well as submitted to regulatory authorities for discussion.

Nursing considerations related to pembrolizumab include monitoring patients closely for symptoms for underlying immune-mediated adverse events (AEs). Liver enzymes, creatinine, and thyroid function should be evaluated at baseline and periodically assessed throughout treatment. In the case of a suspected immune-related AE, alternative etiologies, including infection, should be excluded via appropriate workup.

If interruption or discontinuation is necessary in response to an immune-related AE, systematic corticosteroid therapy should be administered at a dosage of 1 to 2 mg/kg daily until the AE improves to grade 1 or less. Other systematic immunosuppressants may be appropriate for patients whose immune-related AEs are not able to be managed through corticosteroid therapy. Furthermore, drug manufactures urge providers to be cognizant of the risk of colitis, hepatitis, and pneumonitis that can be associated with this immunotherapy.

“The goal of adjuvant treatment is to lower the risk of cancer returning after surgery,” co-principal investigator Luis Paz-Ares, MD, PhD, professor of medicine at Hospital Universitario 12 de Octubre in Madrid, Spain, said. “By moving [pembrolizumab] into earlier stages of non-small cell lung cancer, we may be able to reduce the risk of disease recurrence after surgery for patients with stage IB to IIIA non-small cell lung cancer.”


Merck’s KEYTRUDA (pembrolizumab) showed statistically significant improvement in disease-free survival versus placebo as adjuvant treatment for patients with stage IB-IIIA non-small cell lung cancer regardless of PD-L1 expression. News release. Merck; January 10, 2021. Accessed January 10, 2022.

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