We have detected that you are using an Ad Blocker. PracticeUpdate is free to end users but we rely on advertising to fund our site. Please consider supporting PracticeUpdate by whitelisting us in your ad blocker.
We have sent a message to the email address you have provided, . If this email is not correct, please update your settings with your correct address.
The email address you provided during registration, , does not appear to be valid. Please update your settings with a valid address before to continue using PracticeUpdate.
Welcome to PracticeUpdate! We hope you are enjoying access to a selection of our top-read and most recent articles. Please register today for a free account and gain full access to all of our expert-selected content.
You can find your saved items on your dashboard, in the "saved" tab.
You've recommended your first item
Your recommendations help us improve our content suggestions for you and other PracticeUpdate members.
You've subscribed to your first topic alert
What does that mean?
Each day, we'll check to see if new items have been published to the topics you're subscribed to, and we'll send you one email with all of the new items from that day.
We'll keep all topic alert notifications available on your dashboard for 30 days, to make sure you don't miss anything.
Lastly, whenever you have unread items in the topics you've subscribed to, the "Alerts" icon will light up in the main menu. Just click on the bell to see your five most-recent, unread notifications.
These authors report the final protocol-specified analysis of the KEYNOTE-189 study of platinum/pemetrexed plus pembrolizumab versus platinum/pemetrexed plus placebo in patients with treatment-naive, advanced nonsquamous non–small cell lung cancer (NSCLC). After a median follow-up of 31 months, overall survival (OS) strongly favored the pembrolizumab arm in the entire population and in all PD-L1 subgroups. OS rates at 24 months were 45.7% for the pembrolizumab arm and 27.3% for the placebo arm. Grade 3–5 adverse events were experienced by 72% of patients in the pembrolizumab arm versus 67% of patients in the placebo arm. Of 42 patients completing 2 years of pembrolizumab without experiencing disease progression, 95% were alive at data cutoff.
Long-term follow-up of KEYNOTE-189 reaffirms the profound efficacy and durability of platinum/pemetrexed plus pembrolizumab for advanced nonsquamous NSCLC.
In the phase 3 KEYNOTE-189 study (NCT02578680), pembrolizumab plus pemetrexed and platinum-based chemotherapy (pemetrexed-platinum) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with previously untreated metastatic nonsquamous NSCLC versus placebo plus pemetrexed-platinum. We report updated efficacy outcomes from the protocol-specified final analysis, including outcomes in patients who crossed over to pembrolizumab from pemetrexed-platinum and in patients who completed 35 cycles (approximately 2 years) of pembrolizumab.
Patients and Methods
Eligible patients were randomized 2:1 to pembrolizumab 200 mg (n=410) or placebo (n=206) every 3 weeks (for up to 35 cycles, approximately 2 years) plus 4 cycles of pemetrexed (500 mg/m2) and investigators’ choice of cisplatin (75 mg/m 2) or carboplatin (AUC 5 mg/ml/min) every 3 weeks, followed by pemetrexed until progression. Patients assigned to placebo plus pemetrexed-platinum could crossover to pembrolizumab upon progression if eligibility criteria were met. The primary endpoints were OS and PFS.
After median follow-up of 31.0 months, pembrolizumab plus pemetrexed-platinum continued to improve OS (hazard ratio [HR], 0.56; 95% CI, 0.46‒0.69), and PFS (HR, 0.49; 95% CI, 0.41‒0.59) over placebo plus pemetrexed-platinum regardless of PD-L1 expression. ORR (48.3% versus 19.9%) and time to second/subsequent tumor progression on next-line treatment (PFS2; HR, 0.50; 95% CI, 0.41‒0.61) were improved in patients who received pembrolizumab plus pemetrexed-platinum. 84 patients (40.8%) from the placebo plus pemetrexed-platinum group crossed over to pembrolizumab on-study. Grade 3‒5 adverse events occurred in 72.1% of patients receiving pembrolizumab plus pemetrexed-platinum and 66.8% of patients receiving placebo plus pemetrexed-platinum. 56 patients completed 35 cycles (approximately 2 years) of pembrolizumab; ORR was 85.7% and 53 (94.6%) were alive at data cutoff.
Pembrolizumab plus pemetrexed-platinum continued to show improved efficacy outcomes compared with placebo plus pemetrexed-platinum, with manageable toxicity. These findings support first-line pembrolizumab plus pemetrexed-platinum in patients with previously untreated metastatic nonsquamous NSCLC.
Pemetrexed Plus Platinum With or Without Pembrolizumab in Patients With Previously Untreated Metastatic Nonsquamous NSCLC: Protocol-Specified Final Analysis From KEYNOTE-189
Ann. Oncol 2021 Apr 21;[EPub Ahead of Print], D Rodríguez-Abreu, SF Powell, MJ Hochmair, S Gadgeel, E Esteban, E Felip, G Speranza, F De Angelis, M Dómine, SY Cheng, HG Bischoff, N Peled, M Reck, R Hui, EB Garon, M Boyer, T Kurata, J Yang, MC Pietanza, F Souza, MC Garassino