First Line Combination Immunotherapy Improves Outcomes in Advanced Lung Cancer
by Dr. C.H. Weaver M.D. 1/1/2018
A recently reported study confirms that combination therapy using the “checkpoint inhibitor” Tecentriq®(atezolizumab) and chemotherapy as first line treatment for advanced non-squamous non-small-cell lung cancer (NSCLC) improves progression-free survival (PFS), according to results of the phase III IMpower150 trial.1
About 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) recently approved Keytruda® in combination with Alimta® (pemetrexed) and carboplatin chemotherapy as first-line treatment of metastatic NSCLC, irrespective of PD-L1 expression. Keytruda + Alimta and carboplatin demonstrated an objective response rate of 55% which is nearly nearly double the 29% achieved with chemotherapy alone. The Keytruda regimen also delayed the time to cancer progression from 8.9 months to 13 months extending the overall cancer free survival.2
The IMpower150 clinical trial confirms that combining chemotherapy with immunotherapy improves the treatment of advanced NSCLC. The trial enrolled 1,202 patients who were treated with either chemotherapy plus Tecentriq; chemotherapy plus Tecentriq plus Avastin (bevacizumab); or chemotherapy plus Avastin. Avastin is a biologic anti-angiogenic drug that may enhance the ability of Tecentriq to restore anti-cancer immunity by inhibiting vascular endothelial growth factor (VEGF)-related immunosuppression and other mechanisms while chemotherapy may induce immune responses.
The study demonstrated that the combination of Tecentriq, Avastin, and chemotherapy was superior to Avastin and chemotherapy alone.
These data confirm that the combination of precision cancer immunotherapy using checkpoint inhibitors with chemotherapy will become the new standard initial treatment for many individuals with advanced NSCLC.
1.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.
2.Langer CJ, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17(11):1497–1508.
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