by Dr. C.H. Weaver M.D. updated 6/2019
Keytruda (pembrolizumab) is the first PD-1 Inhibitor to demonstrate improved overall survival when combined with chemotherapy as primary treatment for metastatic non-squamous non-small cell lung cancer (NSCLC).
The KEYNOTE-189 clinical trial evaluated Keytruda in combination with Alimta (pemetrexed) and cisplatin or carboplatin chemotherapy for the first-line treatment of patients with NSCLC. Interim results showed significant improvement in overall survival and progression-free survival for patients receiving Keytruda compared with those receiving chemotherapy alone,
About Non Small Cell Lung Cancer
Lung cancer remains the leading cause of cancer-related deaths worldwide. In the United States, NSCLC accounts for 75–80% of all lung cancers. Although progress has been made in recent years, the majority of patients with advanced stage lung cancer still die from their disease. New treatments are needed. Precision cancer medicines continues to impact the lives of lung cancer patients with research into genomics and genetics leading to unprecedented progress in improving outcomes. Tailored treatments have emerged to match a person’s genetic makeup or a tumor’s genetic profile. As a result, patients with lung cancer now typically receive molecular testing that guides their physicians in determining which therapies are more likely to boost the chances of survival while limiting the potential for adverse effects. Results from studies evaluating immune-modulatory approaches using anti-PD-1 and anti-PD-L1 antibodies have demonstrated promising results and are advancing the standard of care for lung cancer.
Keytruda (pembrolizumab), Tecentriq, and Opdivo (nivolumab) belong to a new class of medicines called “checkpoint inhibitors.” Checkpoint inhibitors are a novel precision cancer immunotherapy that helps to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD-L1 are proteins that inhibit certain types of immune responses, allowing cancer cells to evade detection and attack by certain immune cells in the body. A checkpoint inhibitor can block the PD-1 and PD-L1 pathway and enhance the ability of the immune system to fight cancer. By blocking the binding of the PD-L1 ligand these drugs restore an immune cells’ ability to recognize and fight the colon cancer cells. A diagnostic test to measure the level of PD-L1 is available.
The U.S. Food and Drug Administration (FDA) granted approval for Alimta (pemetrexed) in combination with Keytruda and platinum chemotherapy for the first-line treatment of patients with metastatic non-squamous non–small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations. This indication is approved based on the results of the KEYNOTE 189 clinical trial which enrolled patients regardless of programmed death-ligand 1 (PD-L1) expression.
Alimta in combination with pembrolizumab and carboplatin was first approved in June 2018 under the FDA’s accelerated approval process for the first-line treatment of patients with metastatic non-squamous NSCLC, based on tumor response rates and PFS data from the KEYNOTE 021 clinical trial.
KEYNOTE-189 was a phase III clinical trial performed in 616 patients with previously untreated metastatic non-squamous NSCLC without EGFR or ALK genomic tumor aberrations who were treated with either Alimta in combination with Keytruda and cisplatin or carboplatin chemotherapy or with Alimta in combination with cisplatin or carboplatin.(2)
The overall the response to treatment was improved to 48% from 19% with the addition of Keytruda. The addition of Keytruda also delayed cancer progression from 4.9 to 8.8 months prolonged overall survival.
This was the second clinical study demonstrating that the combination of a checkpoint inhibitor combined with chemotherapy improves treatment outcomes for NSCLC compared to treatment with chemotherapy alone. (3)
- Abstract LBA1_PR ‘Primary PFS and safety analyses of a randomized phase III study of carboplatin + paclitaxel +/− bevacizumab, with or without atezolizumab in 1L non-squamous metastatic NSCLC (IMpower150)‘ will be presented by Martin Reck during the Proffered Paper session ‘Combining immune checkpoint inhibitors and VEGF targeted therapies in cancer treatment’ on Thursday, 7 December, 18:15 to 19:15 (CET) in Room A. Annals of Oncology, Volume 28, 2017 Supplement 11.