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In patients with previously untreated, metastatic, non-squamous non-small cell lung cancer (NSCLC), pembrolizumab plus pemetrexed-platinum has proven to be an effective treatment compared with pemetrexed-platinum alone in increasing the proportion of patients who experience a complete or partial response, as shown in the KEYNOTE-189 study. Based on the results of this study, the FDA recently approved a new indication for pemetrexed in this combination for the first-line treatment of patients with metastatic nonsquamous NSCLC without EGFR or ALK aberrations. But how is patients' quality of life (QOL) affected by this regimen? To answer this question, researchers evaluated patient-reported outcomes (PRO) of participants enrolled in KEYNOTE-189.
The phase 3, multicenter, double-blind, randomized, placebo-controlled KEYNOTE-189 study was conducted at 126 cancer centers spanning 16 countries. To be eligible for this trial, patients had to be aged 18 years or older with histologically or cytologically confirmed metastatic non-squamous NSCLC without sensitizing EGFR or ALK alterations, have measurable disease according to Response Evaluation Criteria in Solid Tumors (version 1.1), and have an Eastern Cooperative Oncology Group performance status of 0 or 1. The researchers enlisted 616 patients and randomly assigned them in a 2:1 ratio to either receive 200 mg intravenous pembrolizumab or saline placebo every 3 weeks for up to 2 years, which equated to 35 cycles. Every patient received four cycles of 500 mg/m2 intravenous pemetrexed with investigator's choice of 5 mg/mL per min carboplatin or 75 mg/m2 cisplatin every 3 weeks for four cycles, followed by pemetrexed maintenance therapy every 3 weeks. A statistics method called permuted block randomization—randomly allocating patients to the treatment group, while maintaining balance across treatment groups—was used with an interactive voice-response system and stratified by PD-L1 expression, choice of platinum, and smoking status.
Patients completed the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (QLQ-C30) and the Lung Cancer 13 (QLQ-LC13) during treatment cycles 1 through 5, in addition to every three cycles thereafter during year 1 and every four cycles during years 2 through 3. The key end points included change from baseline to week 12 during treatment and week 21 after treatment in QLQ-C30 global health status/quality of life (GHS/QOL) score, and time to deterioration in cough, chest pain, or dyspnea.
After a median follow-up of 10.5 months, GHS/QOL scores were maintained from baseline to week 12, with both pembrolizumab plus pemetrexed-platinum and pemetrexed-platinum alone. However, from baseline to week 21, the scores were higher with pembrolizumab plus pemetrexed-platinum compared with pemetrexed-platinum alone (1.3 increase vs 4.0 decrease). On pembrolizumab plus pemetrexed-platinum, median time to decrease in cough, chest pain, or dyspnea was not reached.
"The addition of pembrolizumab to standard chemotherapy maintained GHS/QOL, with improved GHS/QOL scores at week 21 in the pembrolizumab plus chemotherapy group compared with the placebo plus chemotherapy group," the study authors conclude. "These data further support use of pembrolizumab plus pemetrexed-platinum as first-line therapy for patients with metastatic non-squamous non-small cell lung cancer."
For More Information
Garassino MC, Gadgeel S, Esteban E, et al (2020). Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small cell lung cancer (KEYNOTE-189): a multicenter, double-blind, randomized, placebo-controlled, phase 3 trial. Lancet Oncol. [Epub ahead of print] DOI:10.1016/S1470-2045(19)30801-0
Image Courtesy of Yale Rosen. Licensed under CC BY-SA 2.0