The results from an interim analysis of the pivotal, randomized, double-blind, phase 3 KEYNOTE-189 trial comparing the efficacy and safety of platinum-doublet chemotherapy with and without pembrolizumab (Keytruda) for the first-line treatment of patients with metastatic, nonsquamous non–small-cell lung cancer (NSCLC) met the study’s primary outcome measures of progression-free survival (PFS) and overall survival (OS).1 Treatment with the regimen led to significantly longer PFS and OS than pemetrexed plus platinum chemotherapy alone in this patient population, regardless of PD-L1 expression.1
Pembrolizumab is a humanized monoclonal antibody that binds to the PD-1 receptor and blocks the immune-suppressing ligands, PD-L1 and PD-L2, from interacting with PD-1 to aid in restoring T-cell and immune responses.2 Approved by the FDA in several cancer types, pembrolizumab received accelerated approval in May 2017 for the first-line treatment of patients with metastatic, nonsquamous NSCLC, based on tumor response rate and PFS.3 Results from this interim analysis, conducted by the independent Data Monitoring Committee, will be submitted to regulatory authorities for review, and will be presented at an upcoming medical meeting.1
“This approval marks an important milestone in the treatment of lung cancer. Now, pembrolizumab in combination with pemetrexed and carboplatin can be prescribed in the first-line setting for patients with metastatic nonsquamous non–small cell lung cancer, irrespective of PD-L1 expression,” said Corey Langer, MD, Director of Thoracic Oncology and Professor of Medicine, Hospital of the University of Pennsylvania, Philadelphia.3
For the study, investigators enrolled 614 patients aged ≥18 years without EGFR or ALK mutations, with Eastern Cooperative Oncology Group performance status 0 to 1, and who had not received systemic therapy for advanced disease.1,4 Patients were randomized 2:1 to receive 200 mg pembrolizumab plus 500 mg/m2 pemetrexed with vitamin supplementation plus 75 mg/m2 cisplatin or carboplatin AUC 5 on day 1 every 3 weeks (Q3W) for 4 cycles, followed by 200 mg pembrolizumab plus 500 mg/m2 pemetrexed Q3W; or placebo plus 500 mg/m2 pemetrexed with vitamin supplementation plus 75 mg/m2 cisplatin or carboplatin AUC 5 on day 1 Q3W for 4 cycles, followed by placebo plus 500 mg/m2 pemetrexed Q3W until disease progression.1,4,5 Patients receiving placebo who had disease progression verified by central independent review could undergo unblinding to their treatment assignment and receive open-label pembrolizumab.1 All drugs were administered via intravenous infusion.5
The primary outcome measures of PFS (measured by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 as assessed by blinded central imaging) and OS, were both evaluated for a time frame of up to 24 months.5 The study’s secondary outcome measures were overall response rate per RECIST 1.1 as assessed by blinded central imaging for a time frame of up to 24 months, duration of response per RECIST 1.1 as assessed by blinded central imaging for a time frame of up to 24 months, number of patients who experienced an adverse event (AE), evaluated for a time frame of up to 27 months, and number of patients who discontinued study treatment due to an AE, measured for a time frame of up to 24 months.5
In the study regimen, pembrolizumab demonstrated a safety profile consistent with that previously observed.1
1. Merck’s KEYTRUDA® (pembrolizumab) significantly improved overall survival and progression-free survival as first-line treatment in combination with pemetrexed and platinum chemotherapy for patients with metastatic nonsquamous non-small cell lung cancer (KEYNOTE-189). January 16, 2018. www.businesswire.com/news/home/20180116005680/en/Mercks-KEYTRUDA-pembrolizumab-Significantly-Improved-Survival-Progression-Free. Accessed January 23, 2018.
2. Merck. Mechanism of action of KEYTRUDA® (pembrolizumab). www.keytruda.com/hcp/mechanism-of-action/. Accessed January 24, 2018.
3. ASCO Post. FDA approves pembrolizumab as first-line combination therapy with pemetrexed and carboplatin for metastatic nonsquamous NSCLC. May 11, 2017. www.ascopost.com/News/55616. Accessed January 24, 2017.
4. Hall RD, Gadgeel SM, Garon EB, et al. Phase 3 study of platinum-based chemotherapy with or without pembrolizumab for first-line metastatic, nonsquamous non-small cell lung carcinoma (NSCLC): KEYNOTE-189. J Clin Oncol. 34:15 Suppl. DOI: 10.1200/JCO.2016.34.15_suppl.TPS9104. Epub before print.
5. Clinicaltrials.gov. Study of Pemetrexed+Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in Participants With First Line Metastatic Nonsquamous Non-small Cell Lung Cancer (MK-3475-189/KEYNOTE-189). Updated December 1, 2017. www.clinicaltrials.gov/ct2/show/NCT02578680?term=NCT02578680&rank=1. Accessed January 22, 2018.