KEYNOTE 189: Tumor Mutational Burden Not Significantly Associated with Efficacy of Pembrolizumab

Sunday, September 08, 2019

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Chris Martin,CMartin@DavidJamesGroup.com | 630-670-2745
Becky Bunn, MScBecky.Bunn@IASLC.org | 720-325-2946

KEYNOTE 189: Tumor Mutational Burden Not Significantly Associated with Efficacy of Pembrolizumab

Barcelona— Tumor mutational burden was not significantly associated with efficacy of pembrolizumabplus chemotherapy or placebo plus chemotherapy as first-line therapy for metastatic nonsquamousnon-small cell lung cancer, according to research reported today by Dr. M. Garassino from theFondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Dr. Garassino presented this new datatoday at the IASLC 2019 World Conference on Lung Cancer hosted by the International Association forthe Study of Lung Cancer. 

Tumor mutational burden is a measurement of mutations carried by tumor cells and is a predictivebiomarker being studied to evaluate its association with response to immunotherapy. TMB, in concertwith PD-L1 expression, has been demonstrated to be a useful biomarker across some cancer types.

To test this notion, Dr. Garassino and her colleagues randomized 616 patients 2:1 to pembrolizumabplus chemotherapy or placebo plus chemotherapy. TMB was determined by whole-exome sequencing oftumor and matched normal DNA. The clinical utility of TMB on outcomes was assessed usingprespecified TMB cut points of 175 and 150 Mut/.

Of the 616 patients enrolled, 293 (48.3%) had evaluable TMB data: 207 for pembrolizumab pluschemotherapy, 86 for placebo plus chemotherapy. Baseline characteristics and outcomes were generallysimilar in the TMB-evaluable and total populations. TMB as a continuous variable was not significantlyassociated with overall survival, progression-free survival or objective response rate for pembrolizumabplus chemotherapy or placebo plus chemotherapy. Pembrolizumab plus chemotherapy improved overallsurvival, progression-free survival and objective response rate.

“Tumor mutational burden was not significantly associated with efficacy of pembrolizumab pluschemotherapy or placebo plus chemotherapy as first-line therapy for metastatic nonsquamous NSCLC,”said Dr. Garassino. “Pembrolizumab plus chemotherapy had a similar OS benefit in the TMB-high andlow subgroups.”

About the WCLC:
The WCLC is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies,attracting more than 7,000 researchers, physicians and specialists from more than 100 countries. Thegoal is to increase awareness, collaboration and understanding of lung cancer, and to help participantsimplement the latest developments across the globe. The conference will cover a wide range ofdisciplines and unveil several research studies and clinical trial results. For more information, visit wclc2019.iaslc.org.

About the IASLC:

The International Association for the Study of Lung Cancer (IASLC) is the only global organizationdedicated solely to the study of lung cancer and other thoracic malignancies. Founded in 1974, theassociation's membership includes more than 7,500 lung cancer specialists across all disciplines in over100 countries, forming a global network working together to conquer lung and thoracic cancersworldwide. The association also publishes the Journal of Thoracic Oncology, the primary educational andinformational publication for topics relevant to the prevention, detection, diagnosis and treatment of allthoracic malignancies. Visit www.iaslc.org for more information. 

About the Author

Chris Martin, Vice President, Public Relations