Currently Viewing:
American Society of Clinical Oncology Annual Meeting
Persephone Trial: Cutting Trastuzumab Duration by Half Safer, Efficacious in HER2-Positive Breast Cancer
May 29, 2018
Remote Monitoring Can Reduce Radiation-Related Symptoms in Head and Neck Cancer
May 30, 2018
Despite USPSTF Recommendations, Lung Screening Rates Low Among Heavy Smokers
May 31, 2018
Nelarabine With Chemotherapy Boosted Outcomes in Pediatric and YA Patients With T-Cell Cancers
June 01, 2018
Dr Leonard B. Saltz on Deciding When a Patient Should Receive NGS Testing
June 02, 2018
Promising Early Phase Results With bb2121 CAR T Treatment in Relapsed Refractory Multiple Myeloma
June 02, 2018
Dr Peter Paul Yu Discusses the Impact of Health Information Technology in Oncology
June 02, 2018
Identifying Rational Immunotherapy Combinations for Glioblastoma: A Progress Report
June 02, 2018
Dr James Lin Chen Outlines Information Needs in Era of Precision Medicine
June 02, 2018
Ellen Miller Sonet Highlights Financial Burdens of Patients With Cancer
June 02, 2018
Utilization Management in Oncology: Current Strategies and a Path Forward
June 02, 2018
Immune Checkpoint Inhibitors Improve Outcomes in Mismatch Repair Deficient CRC, but Can Induce irAEs
June 02, 2018
ZUMA-1: Response to Axi-cel at Three Months Prognostic for Remission in B-cell Lymphoma
June 03, 2018
Cetuximab With Chemoradiation Worse Than Chemoradiation Alone in Older Patients With HNSCC
June 03, 2018
Dr Michael Thompson: The Role of Precision Medicine in the Community Setting
June 03, 2018
Dr Victoria Villaflor Outlines Challenges With Pursuing Precision Medicine
June 03, 2018
Clinical Trials: Sharing the Road With Real-World Evidence
June 04, 2018
Phase 3 TAILORx Results Confirm Chemotherapy Unnecessary in 70% of Women With Early-Stage Breast Cancer
June 04, 2018
Currently Reading
KEYNOTE-042 Confirms First-Line Pembrolizumab Superior to Chemotherapy in PD-L1–Low Advanced NSCLC
June 04, 2018
Nearly Half of Patients With Metastatic CSCC Respond to Cemiplimab, on Fast Track at FDA
June 04, 2018
Opdivo Plus Chemo Boosts Progression-Free Survival 26% Over Chemo Alone in Late-Stage NSCLC
June 04, 2018
Managing Cancer-Related Pain in the Era of the Opioid Crisis
June 06, 2018
Discussing the Cost Burden of Cancer With Patients
June 06, 2018
Study Underscores Value of PROs in Improving Lung Cancer Survival
June 07, 2018

KEYNOTE-042 Confirms First-Line Pembrolizumab Superior to Chemotherapy in PD-L1–Low Advanced NSCLC

Surabhi Dangi-Garimella, PhD
A late-breaking abstract presented on Sunday at the 2018 American Society of Clinical Oncology Annual Meeting confirmed that pembrolizumab significantly improved the primary endpoint of overall survival over platinum-based chemotherapy in treatment-naïve advanced/metastatic non–small cell lung cancer (NSCLC). The effect, the authors found, was agnostic of PD-L1 expression, meaning the monoclonal antibody was effective for tumors expressing PD-L1 at ≥50%, ≥20%, and ≥1%.
A late-breaking abstract presented Sunday at the 2018 American Society of Clinical Oncology Annual Meeting confirmed that pembrolizumab significantly improved the primary endpoint of overall survival (OS) over platinum-based chemotherapy in treatment-naïve advanced/metastatic non–small cell lung cancer (NSCLC). The effect, the authors found, was agnostic of PD-L1 expression, meaning the monoclonal antibody was effective for tumors expressing PD-L1 at ≥50%, ≥20%, and ≥1%.1

However, the secondary outcome of progression-free survival (PFS) was not met at data cut-off on February 26, 2018.

Pembrolizumab monotherapy has shown significant improvement in OS over docetaxel as second-line treatment in metastatic NSCLC with PD-L1 tumor proportion score (TPS) ≥1%. Additionally, patients whose NSCLC had a PD-L1 TPS of ≥50% saw significant improvements in both PFS and OS with first-line pembrolizumab, compared to platinum-based chemotherapy (KEYNOTE-024).

Results from the Keynote-189 study, published earlier this year, emphasized the advantage of combining chemotherapy with pembrolizumab: the researchers showed that the combination approach as first-line in patients with metastatic NSCLC, without EGFR or ALK alterations, was significantly better than chemotherapy alone and was agnostic of PD-L1 expression.2

“Our trial, Keynote-042, is evaluating pembrolizumab monotherapy against platinum-based chemotherapy for metastatic NSCLC with low expression of PD-L1,” said lead author Gilberto Lopes, MD, MBA, Sylvester Comprehensive Cancer Center, University of Miami Health System. The trial was designed to develop a more effective and tolerable first-line treatment for metastatic NSCLC, he said.

Eligibility criteria included locally advanced or metastatic tumors with PD-L1 TPS ≥1%, without EGFR or ALK alterations. The Eastern Cooperative Oncology Group or ECOG status had to be 0 or 1; patients had to be free of untreated or unstable CNS metastases.  

Treatment-eligible patients were randomized 1:1 to ≤35 cycles of pembrolizumab 200 mg every 3 weeks or investigator’s choice of ≤6 cycles of paclitaxel + carboplatin or pemetrexed + carboplatin with optional pemetrexed maintenance (nonsquamous only). Primary end-points were OS in pts with TPS ≥50%, ≥20%, and ≥1%. Secondary endpoints were PFS and objective response rate for all 3 TPS; safety in TPS ≥1%.

At 12.8-months median follow-up, 13.7% of patients were still on pembrolizumab and 4.9% were receiving pemetrexed maintenance treatment.

In the TPS ≥50% subset, median OS at 24 months was 20 months (range, 15.4-24.9) in the pembrolizumab-treated patients (event rate: 44.7%) and 12.2 months (range, 10.4-14.2) in those treated with chemotherapy (event rate: 30.1%). Similarly, in the TPS ≥20% subset, median OS at 24 months was 17.7 months (range, 15.3-22.1) in the pembrolizumab-treated patients (event rate: 40.5%) and 13.0 months (range, 11.6-15.3) in those treated with chemotherapy (event rate: 29.6%). Among patients whose tumors expressed a low level of PD-L1 (TPS ≥1%), median OS at 24 months was 16.7 months (range, 13.9-19.7) in the pembrolizumab-treated arm (event rate: 39.3%) and 12.1 months (range, 11.3-13.3) in those treated with chemotherapy (event rate: 28.0%).

Lopes shared the PFS data in the TPS ≥20% cohort. Median PFS at 12 months was 6.2 months (range, 5.1-7.8) in the pembrolizumab-treated arm (event rate: 32.4%) and 6.6 months (range, 6.2-7.3) in those treated with chemotherapy (event rate: 28.8%).

Grade 3-5 drug-related adverse events were less frequent with pembrolizumab, Lopes said (17.8% vs 41.0% for chemotherapy). However, the rate of discontinuation (about 9.0%) and treatment-related deaths (about 2.0%) were similar between the 2 groups. Immune-related adverse events or irAEs are a significant concern with using immune checkpoint inhibitors such as pembrolizumab. Lopes shared that about 27.8% of patients treated with pembrolizumab experienced irAEs, and 1 patient died as a result. Only 7% of patients in the chemotherapy arm had irAE flare-ups.

“Keynote-042 is the first study with a primary end-point of overall survival to demonstrate superiority of pembrolizumab over platinum-based chemotherapy in patient with previously untreated advanced/metastatic NSCLC without sensitizing EGFR or ALK alterations and a PD-L1 TPS ≥1%,” the authors concluded.

“Our data confirm and potentially extend the role of pembrolizumab monotherapy as a standard first-line treatment for patients with PD-L1–expressing tumors,” said Lopes. He shared that based on the advice of their external drug monitoring committee, the trial continues to evaluate PFS in this trial population.

Leena Gandhi, MD, currently the director of Thoracic Medical Oncology and an associate professor of medicine at the New York University School of Medicine, who will soon be joining Eli Lilly and Company, was the discussant for this abstract.

Comparing the performance of nivolumab, the other PD-1 inhibitor, with pembrolizumab, Gandhi questioned whether the crossover allowed in the Checkmate-026 study may have resulted in the failure of nivolumab as first-line treatment in advanced/metastatic NSCLC. “Overall, the studies are more similar than they are different,” she said. However, Checkmate-026 allowed 60.4% of patients in the chemotherapy arm to cross over to the nivolumab arm, whereas only 19.8% in Keynote-042 who received chemotherapy were subsequently treated with pembrolizumab.

She identified several caveats with the Keynote-042 results:
  • The benefit is driven with high PD-L1 expressors
  • PD-L1 expression has high clinical utility and should be used, but it could be complemented by following TMB expression in the tumor samples
  • She advised researchers to analyze the tumor microenvironment
References
  1. Lopes G, Wu Y, Kudaba I, et al. Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 1%: Open-label, phase 3 KEYNOTE-042 study. J Clin Oncol. 2018;36(suppl; abstract LBA4).
  2. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al; Keynote-189 investigators. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378(22):2078-2092. doi: 10.1056/NEJMoa1801005.


Related Articles

Pembrolizumab Now Approved for First-Line Treatment of Lung Cancer in Europe and the US
Pembrolizumab Plus Chemotherapy Approved for Metastatic Nonsquamous NSCLC
FDA Grants Priority Review for Pembrolizumab, Chemotherapy Combination in NSCLC
Pembrolizumab Improved OS, PFS as First-Line Treatment in NSCLC
 
Copyright AJMC 2006-2018 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
x
Welcome the the new and improved AJMC.com, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up
×

Sign In

Not a member? Sign up now!