KEY TAKEAWAYS
- This phase 3 clinical trial MK-3475-042/KEYNOTE-042 aimed to compare the OS of patients with locally advanced/metastatic NSCLC without EGFR/ALK alterations.
- Patients were randomly assigned to receive pembrolizumab or chemotherapy (carboplatin + paclitaxel or pemetrexed).
- Pembrolizumab was superior to chemotherapy for OS for TPS ≥ 50%, with estimated 5-year OS rates of 21.9%, 19.4%, and 16.6%.
- The study revealed that pembrolizumab monotherapy showed lasting clinical benefit in PD-L1-positive, locally advanced/metastatic NSCLC without EGFR/ALK mutations.
Multiple endpoints with varying maturation durations are standard in clinical trials. Even if the results from the anticipated co-primary or secondary analyses are not yet available, the initial report may be released if it is based on the primary endpoint. When the primary endpoint has been disclosed, new results from a study published in the Journal of Clinical Oncology (JCO) or elsewhere can be disseminated through Clinical Trial Updates. Researchers presented data from the KEYNOTE-042 research conducted over five years (NCT02220894 on ClinicalTrials.gov).
Pembrolizumab 200 mg once every three weeks for 35 cycles or chemotherapy (carboplatin + paclitaxel or pemetrexed) for 4-6 cycles with optional maintenance pemetrexed was given to patients with locally advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations and with Programmed Death Ligand-1 (PD-L1) tumor proportion score (TPS) ≥ 1%. The preliminary endpoint was overall survival (OS) in subgroups defined by PD-L1 TPS levels of ≥ 50%, ≥ 20%, and ≥ 1%.
A second course of pembrolizumab might be initiated in patients who have completed 35 cycles of the drug with stable illness. About 1,274 patients (637 people given pembrolizumab and 637 people given chemotherapy) were split evenly between the two groups. The average duration of the follow-up was 61.1 months (range: 50.0-76.3). Pembrolizumab was superior to chemotherapy for overall survival (hazard ratio [95% CI] for TPS ≥ 50%, 0.68 [0.57 to 0.81]; TPS ≥ 20%, 0.75 [0.64 to 0.87]; TPS ≥ 1%, 0.79 [0.70 to 0.89]), with estimated 5-year OS rates of 21.9%, 19.4%, and 16.6%. There were no undiscovered toxicity issues. Among 102 patients who finished 35 cycles of pembrolizumab, 84.3% had an objective response, but the rate for 33 patients who received a second course of pembrolizumab was only 15.2%. In PD-L1-positive, locally advanced/metastatic NSCLC without EGFR/ALK mutations, pembrolizumab monotherapy shows lasting clinical benefit against chemotherapy after five years of follow-up.
Source:https://pubmed.ncbi.nlm.nih.gov/36306479/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT02220894
de Castro G Jr, Kudaba I, Wu YL, Lopes G, Kowalski DM, Turna HZ, Caglevic C, Zhang L, Karaszewska B, Laktionov KK, Srimuninnimit V, Bondarenko I, Kubota K, Mukherjee R, Lin J, Souza F, Mok TSK, Cho BC. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy as First-Line Therapy in Patients With Non-Small-Cell Lung Cancer and Programmed Death Ligand-1 Tumor Proportion Score ≥ 1% in the KEYNOTE-042 Study. J Clin Oncol. 2023 Apr 10;41(11):1986-1991. doi: 10.1200/JCO.21.02885. Epub 2022 Oct 28. PMID: 36306479; PMCID: PMC10082298.
