Journal ArticleDOI
First FDA Approval Agnostic of Cancer Site - When a Biomarker Defines the Indication.
TLDR
In May 2017, the FDA approved pembrolizumab, a programmed death 1 inhibitor, for adult and pediatric patients with unresectable or metastatic, microsatellite-instability–high or mismatch-repair–deficient solid tumors, regardless of tumor site or histology.Abstract:
In May 2017, the FDA approved pembrolizumab, a programmed death 1 inhibitor, for adult and pediatric patients with unresectable or metastatic, microsatellite-instability–high or mismatch-repair–deficient solid tumors, regardless of tumor site or histology.read more
Citations
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Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic
Timothy A. Chan,Mark Yarchoan,Elizabeth M. Jaffee,Charles Swanton,Sergio A. Quezada,Albrecht Stenzinger,Solange Peters +6 more
TL;DR: TMB, in concert with PD-L1 expression, has been demonstrated to be a useful biomarker for ICB selection across some cancer types; however, further prospective validation studies are required.
Journal ArticleDOI
Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study.
Aurélien Marabelle,Dung T. Le,Paolo A. Ascierto,Anna Maria Di Giacomo,Ana De Jesus-Acosta,Jean Pierre Delord,Ravit Geva,Maya Gottfried,Nicolas Penel,Aaron R. Hansen,Sarina Anne Piha-Paul,Toshihiko Doi,Bo Gao,Hyun Cheol Chung,Jose A. Lopez-Martin,Yung-Jue Bang,Ronnie Shapira Frommer,Manisha H. Shah,Razi Ghori,Andrew K. Joe,Scott K. Pruitt,Luis A. Diaz +21 more
TL;DR: The study demonstrates the clinical benefit of anti-programmed death-1 therapy with pembrolizumab among patients with previously treated unresectable or metastatic MSI-H/dMMR noncolorectal cancer.
Journal ArticleDOI
Top 10 Challenges in Cancer Immunotherapy
Priti S. Hegde,Daniel S. Chen +1 more
TL;DR: Ten key challenges facing cancer immunotherapy are defined, which range from lack of confidence in translating pre-clinical findings to identifying optimal combinations of immune-based therapies for any given patient.
Journal ArticleDOI
FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors
TL;DR: The FDA approved pembrolizumab for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H), or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Journal ArticleDOI
Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability–High/Mismatch Repair–Deficient Metastatic Colorectal Cancer: KEYNOTE-164
Dung T. Le,Tae Won Kim,Eric Van Cutsem,Ravit Geva,Dirk Jäger,Hiroki Hara,Matthew Burge,Bert H. O'Neil,Petr Kavan,Takayuki Yoshino,Rosine Guimbaud,Hiroya Taniguchi,Elena Elez,Salah-Eddin Al-Batran,Patrick McKay Boland,Todd S. Crocenzi,Chloe E. Atreya,Yi Cui,Tong Dai,Patricia Marinello,Luis A. Diaz,Thierry André +21 more
TL;DR: Pembrolizumab is effective with a manageable safety profile in patients with MSI-H/dMMR CRC, and the primary end point was objective response rate by RECIST version 1.1 by independent central review.
References
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Journal ArticleDOI
Classification and characterization of microsatellite instability across 18 cancer types
TL;DR: A correlation between survival outcomes and the overall burden of unstable microsatellites is observed, suggesting that MSI may be a continuous, rather than discrete, phenotype that is informative across cancer types.
Journal ArticleDOI
Microsatellite Instability as a Biomarker for PD-1 Blockade
TL;DR: A review of the pathogenesis and prognostic value of MSI, diagnostic guidelines for detecting it, and the frequency of MSI across tumors, with the goal of providing a reference for its use as a biomarker for PD-1 blockade.
Journal ArticleDOI
Phase II Pilot Study of Vemurafenib in Patients With Metastatic BRAF-Mutated Colorectal Cancer.
Scott Kopetz,Jayesh Desai,Emily Chan,J. R. Hecht,Peter J. O'Dwyer,Dipen M. Maru,Van K. Morris,Filip Janku,Arvind Dasari,Woonbook Chung,Jean Pierre J. Issa,Peter Gibbs,Peter Gibbs,Brian P. James,Garth Powis,K. B. Nolop,Suman Bhattacharya,Leonard B. Saltz +17 more
TL;DR: Single-agent vemurafenib did not show meaningful clinical activity in patients with BRAF V600E mutant CRC, and combination strategies are now under development and may be informed by the presence of intratumor heterogeneity of KRAS and NRAS mutations.
Journal ArticleDOI
Mismatch Repair Status and BRAF Mutation Status in Metastatic Colorectal Cancer Patients: A Pooled Analysis of the CAIRO, CAIRO2, COIN, and FOCUS Studies
Sabine Venderbosch,Iris D. Nagtegaal,Tim Maughan,Christopher Smith,Jeremy Peter Cheadle,David Fisher,Richard Kaplan,Philip Quirke,Matthew T. Seymour,Susan D. Richman,Gerrit A. Meijer,Bauke Ylstra,Daniëlle A.M. Heideman,Anton F.J. de Haan,Cornelis J. A. Punt,Miriam Koopman +15 more
TL;DR: The data suggest that the poor prognosis of dMMR is driven by the BRAFMT status, and both biomarkers confer an inferior prognosis.
Proceedings ArticleDOI
Abstract PD2-08: Neratinib + fulvestrant inERBB2-mutant, HER2–non-amplified, estrogen receptor (ER)-positive, metastatic breast cancer (MBC): Preliminary analysis from the phase II SUMMIT trial
David M. Hyman,Sarina Anne Piha-Paul,Cristina Saura,CL Arteaga,IA Mayer,Geoffrey I. Shapiro,Sherene Loi,Alshad S. Lalani,Feng Xu,Richard E. Cutler,Anna Butturini,Richard A. Bryce,Funda Meric-Bernstam,J. Baselga,David B. Solit +14 more
TL;DR: Clinical efficacy in the ER+ MBC cohort met pre-specified efficacy requirements; a confirmatory trial of neratinib + fulvestrant for targeting ERBB2 mutations in ER-mutant breast cancer is warranted.
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