According to an interim analysis of the Phase 3 trial KEYNOTE-091 (also known as EORTC -1416-LCG/ETOP-8-15 – PEARLS [NCT02504372]).¹ Notably, the observed significant improvement over placebo, which met the primary endpoint of the trial, was seen in all participants regardless of PD-L1 expression.

Interim results demonstrated that patients whose tumors expressed PD-L1 with a Tumor Proportion Score (TPS) of 50% or greater had improved SSM after treatment with pembrolizumab, however, there was no enough statistically significant results related to this dual primary endpoint according to the predefined statistical plan. Researchers will continue to assess SSM in patients whose tumors harbor high levels of PD-L1 and assess overall survival (OS) as a key secondary endpoint.

Pembrolizumab is an anti-programmed death receptor 1 (PD-1) therapy that works by blocking the interaction between PD-1 and its ligands PD-L1 and PD-L2, thereby activating T cells and boosting the immune system of the body to help detect and fight tumor cells. KEYNOTE-091 represents the first positive trial to evaluate this agent in the adjuvant setting of NSCLC, which is known to be the most common form of lung cancer and 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, it is estimated that 43% of those who have surgery will have their disease return,” said co-lead researcher Mary O’Brien, MD, FRCP, The Royal Marsden, NHS Foundation Trust, and Professor at Imperial College of London, UK. in a press release. “KEYNOTE-091 data suggests an adjuvant [pembrolizumab] reduces 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 pembrolizumab 200 mg 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 previously undergone surgical resection (either lobectomy or pneumonectomy). DFS was calculated as time from randomization to date of disease recurrence, onset of second primary lung cancer, onset of second primary cancer, or death in any event cause, whichever comes first.

The safety profile of pembrolizumab was found to be consistent with previously reported data. However, the full results should be presented at an upcoming medical meeting, as well as submitted to regulatory authorities for discussion.

Nursing considerations with pembrolizumab include close monitoring of patients for symptoms of underlying immune-mediated adverse events (AEs). Liver enzymes, creatinine, and thyroid function should be assessed initially and periodically during treatment. If immune-mediated AE is suspected, other etiologies, including infection, should be excluded through appropriate workup.

If interruption or discontinuation is necessary in response to an immune-mediated AE, routine corticosteroid therapy should be given at a dosage of 1 to 2 mg/kg daily until the AE improves to grade 1 or less. Other systemic immunosuppressants may be appropriate for patients whose immune-related AEs cannot be managed with corticosteroid therapy. Additionally, drug manufacturers urge providers to be aware of the risk of colitis, hepatitis, and pneumonitis that may be associated with this immunotherapy.

“The goal of adjuvant therapy is to reduce the risk of cancer recurrence after surgery,” said co-lead researcher Luis Paz-Ares, MD, PhD, professor of medicine at 12 de Octubre University Hospital in Madrid. , in Spain. “By moving [pembrolizumab] in the early 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.

Reference

KEYTRUDA (pembrolizumab) from Merck has shown a statistically significant improvement in disease-free survival compared to placebo as an adjuvant therapy for patients with stage IB-IIIA non-small cell lung cancer, regardless of age. expression of PD-L1. Press release. Merck; January 10, 2021. Accessed January 10, 2022. https://bit.ly/3zJssg7