Researchers presented full results of Keytruda® (pembrolizumab) and Opdivo® (nivolumab) in previously untreated advanced non-small cell lung cancer (NSCLC) at the European Society for Medical Oncology annual meeting in Copenhagen. An additional study was also recently published in the New England Journal of Medicine evaluating Keytruda in previously treated patients with advanced NSCLC .
Results of the ESMO study indicate that treatment with Keytruda for previously untreated advanced NSCLC whose tumors expressed high levels of PD-1 is superior to standard chemotherapy.1 The study evaluating Opdivo did not find that the drug improved outcomes compared to chemotherapy, but this could have been due to patient selection.2
Precision medicine 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 immunomodulatory approaches using anti-PD-1 and anti-PD-L1 antibodies have demonstrated promising results and are advancing the standard of care for lung cancer.
PD-1 is a protein that inhibits certain types of immune responses. Drugs that block PD-1, such as Keytruda and Opdivo, may enhance the ability of the immune system to fight cancer. In earlier studies Keytruda has demonstrated anticancer activity in advanced lung cancer.3,4 Both Keytruda and Opdivo are approved in the U.S. to treat lung-cancer patients whose disease has progressed after prior chemotherapy treatment and for some other tumors.5,6
In the ESMO study, Keytruda was evaluated in patients with previously untreated NSCLC and compared to standard platinum chemotherapy. Overall nearly 45% of patients receiving Keytruda experienced significant tumor shrinkage, versus 28% of the chemotherapy patients, ~ 80% of patients who took Keytruda were alive six months after the start of treatment, compared with 72% of those on chemotherapy. Keytruda also extended the time until death or disease progression to an average of 10.3 months compared to 6 months for chemotherapy. Severe side effects occurred at a higher rate among chemotherapy patients.
The Keytruda study results could impact a new standard of care for first-line treatment of advanced NSCLC cancer patients whose tumors have high levels of PD-L1.
Results from a study evaluating Opdivo as a first-line treatment in a broader patient pool found no significant difference in overall survival or progression-free survival between the groups.
The divergent outcomes between the Keytruda and Opdivo studies may be the result of patient selection; the Keytruda study only enrolled patients with high levels of PD-L1, whereas Opdivo also included patients with lower levels.
In a separate study, NSCLC patients receiving the PD-L1 checkpoint inhibitor Tecentriq® (atezolizumab) after prior treatments had a median survival of 13.8 months, compared with 9.6 months for patients on chemotherapy. Patients in this study had failed one or two prior treatments and were eligible for the study whether or not they expressed the PD-L1 biomarker. Tecentriq is already approved for advanced bladder cancer and the FDA is currently reviewing Tecentriq for second-line NSCLC.7
- Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. N Engl J Med. DOI: 10.1056/NEJMoa1606774
- ESMO. (2016.) Greater patient selection may be needed for first line nivolumab to improve progression-free survival in advanced lung cancer. Accessed Oct 9. 2016. http://www.alphagalileo.org/ViewItem.aspx?ItemId=168743&CultureCode=en
- Merck’s KEYTRUDA (pembrolizumab) demonstrates superior progression-free and overall survival compared to chemotherapy as first line treatment in patients with advanced non-small cell lung cancer. [Press release.] http://www.mercknewsroom.com/news-release/oncology-newsroom/mercks-keytruda%C2%A0pembrolizumab-demonstrates-superior-progression-free- Accessed June 21, 2016.
- Gadgeel SM, Stevenson J, Langer C, et al. Pembrolizumab (pembro) plus chemotherapy as front-line therapy for advanced NSCLC: KEYNOTE-021 cohorts A-C. J Clin Oncol 34, 2016 (suppl; abstr 9016).
- Kawaguchi T, Ando M, Asami K, et al. Randomized Phase III Trial of Erlotinib Versus Docetaxel As Second- or Third-Line Therapy in Patients With Advanced Non–Small-Cell Lung Cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA). J Clin Oncol 2014;32:1902-1908.
- Roche. (2016.) Roche’s TECENTRIQ (atezolizumab) shows significant survival advantage compared to chemotherapy regardless of PD-L1 status in a specific type of lung cancer in Phase III study. [Press release.] Can be retrieved from http://www.roche.com/dam/jcr:925023c8-5597-4d82-8b4e-3d10bcd7c6f9/en/med-cor-2016-10-09-e.pdf
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