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Response to rapamycin analogs but not PD-1 inhibitors in PTEN-mutated metastatic non-small-cell lung cancer with high tumor mutational burden

Authors Parikh AR, Ali SM, Schrock AB, Albacker LA, Miller VA, Stephens PJ, Crilley P, Markman M

Received 6 January 2018

Accepted for publication 1 February 2018

Published 18 May 2018 Volume 2018:9 Pages 45—47


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Sai-Hong Ignatius Ou

Video abstract presented by Ankur R Parikh.

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Ankur R Parikh,1 Siraj M Ali,2 Alexa B Schrock,2 Lee A Albacker,2 Vincent A Miller,2 Phil J Stephens,2 Pamela Crilley,1 Maurie Markman1

1Eastern Regional Medical Center, Cancer Treatment Centers of America, Philadelphia, PA, USA; 2Foundation Medicine, Inc, Cambridge, MA, USA

Abstract: In non-small-cell lung cancer (NSCLC) refractory to standard therapy and which lacks well-known oncogenic drivers, genomic profiling can still identify genomic alterations that may suggest potential sensitivity to targeted therapy. PTEN mutation in NSCLC may be sensitizing to analogs of rapamycin such as everolimus or temsirolimus, but more investigation is needed. We report the case of a patient with metastatic NSCLC harboring a PTEN mutation as well as high tumor mutational burden and PD-L1 positivity with a durable response to temsirolimus, but refractory to a checkpoint inhibitor. Even in the event of failure of treatment with checkpoint inhibitors in the background of a case with a higher tumor mutational burden and PD-L1 positivity, targeting specific genomic alterations may still result in patient benefit.

Keywords: genomic profiling, temsirolimus, targeted therapy, immunotherapy

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