| Abstract: |
PURPOSE Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard first-line therapy for EGFR-mutant, metastatic non-small cell lung cancer (NSCLC); however, most patients experience disease progression.We report results from the randomized, double-blind, phase III KEYNOTE-789 study of pemetrexed and platinum-based chemotherapy with or without pembrolizumab for TKI-resistant, EGFR-mutant, metastatic nonsquamous NSCLC (ClinicalTrials.gov identifier: NCT03515837).METHODS Adults with pathologically confirmed stage IV nonsquamous NSCLC, documented DEL19 or L858R EGFR mutation, and progression after EGFR-TKI treatment were randomly assigned 1:1 to 35 cycles of pembrolizumab 200 mg or placebo once every 3 weeks plus four cycles of pemetrexed and carboplatin or cisplatin once every 3 weeks and then maintenance pemetrexed.Dual primary end points were progression-free survival (PFS) and overall survival (OS).Final PFS testing was completed at the second interim analysis (IA2; data cutoff, December 3, 2021); OS was tested at final analysis (FA; data cutoff, January 17, 2023).Efficacy boundaries were one-sided P 5.0117 for PFS and OS.RESULTS Four hundred ninety-two patients were randomly assigned to pembrolizumab plus chemotherapy (n 5 245) or placebo plus chemotherapy (n 5 247).At IA2, the median PFS was 5.6 months for pembrolizumab plus chemotherapy versus 5.5 months for placebo plus chemotherapy (hazard ratio [HR], 0.80 [95% CI, 0.65 to 0.97]; P 5.0122).At FA, the median OS was 15.9 versus 14.7 months, respectively (HR, 0.84 [95% CI, 0.69 to 1.02]; P 5.0362).Grade ≥3 treatment-related adverse events occurred in 43.7% of pembrolizumab plus chemotherapy recipients versus 38.6% of placebo plus chemotherapy recipients.CONCLUSION Addition of pembrolizumab to chemotherapy in patients with TKI-resistant, EGFR-mutant, metastatic nonsquamous NSCLC did not significantly prolong PFS or OS versus placebo plus chemotherapy in KEYNOTE-789. © 2024 by American Society of Clinical Oncology. |
| Keywords: |
adult; cancer survival; controlled study; aged; aged, 80 and over; middle aged; major clinical study; overall survival; genetics; mutation; clinical trial; constipation; fatigue; mortality; hepatitis; cisplatin; placebo; cancer combination chemotherapy; side effect; skin manifestation; antineoplastic agent; carboplatin; metastasis; progression free survival; multiple cycle treatment; anemia; protein kinase inhibitor; nausea; randomized controlled trial; vomiting; antineoplastic combined chemotherapy protocols; carcinoma, non-small-cell lung; lung neoplasms; epidermal growth factor receptor; drug resistance; pathology; drug resistance, neoplasm; tyrosine kinase inhibitors; monoclonal antibody; protein tyrosine kinase inhibitor; alanine aminotransferase blood level; aspartate aminotransferase blood level; asthenia; pneumonia; protein kinase inhibitors; lung tumor; alanine aminotransferase; aspartate aminotransferase; multicenter study; platinum; phase 3 clinical trial; hyperthyroidism; hypothyroidism; drug therapy; insulin dependent diabetes mellitus; double blind procedure; double-blind method; pemetrexed; egfr protein, human; non small cell lung cancer; progression-free survival; adrenal insufficiency; bone marrow depression; decreased appetite; thyroiditis; myelitis; nephritis; myocarditis; erbb receptors; antibodies, monoclonal, humanized; maintenance chemotherapy; immune mediated injury; infusion related reaction; very elderly; humans; human; male; female; article; pembrolizumab; osimertinib
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