TY - JOUR
T1 - Characteristics and outcome of AKT1E17K - mutant breast cancer defined through AACR project GENIE, a clinicogenomic registry
AU - AACR Project GENIE Consortium
AU - Smyth, Lillian M.
AU - Zhou, Qin
AU - Nguyen, Bastien
AU - Yu, Celeste
AU - Lepisto, Eva M.
AU - Arnedos, Monica
AU - Hasset, Michael J.
AU - Lenoue-Newton, Michele L.
AU - Blauvelt, Natalie
AU - Dogan, Semih
AU - Micheel, Christine M.
AU - Wathoo, Chetna
AU - Horlings, Hugo
AU - Hudecek, Jan
AU - Gross, Benjamin E.
AU - Kundra, Ritika
AU - Sweeney, Shawn M.
AU - Gao, Jian Jiong
AU - Schultz, Nikolaus
AU - Zarski, Andrew
AU - Gardos, Stuart M.
AU - Lee, Jocelyn
AU - Sheffler-Collins, Seth
AU - Park, Ben H.
AU - Sawyers, Charles L.
AU - André, Fabrice
AU - Levy, Mia
AU - Meric-Bernstam, Funda
AU - Bedard, Philippe L.
AU - Iasonos, Alexia
AU - Schrag, Deborah
AU - Hyman, David M.
N1 - Funding Information:
L.M. Smyth is consultant for Roche Genentech, Pfizer, and Novartis, reports receiving commercial research grants from Astra-Zeneca, Puma Biotechnology Inc., and Roche Genentech, and has received other remuneration from AstraZeneca, Roche Genentech, Pfizer, and Puma Biotechnology Inc. M. Arnedos reports receiving commercial research support from Lilly and has received honoraria from the speakers bureaus of Novartis, AstraZeneca, and Seattle Genetics. C.M. Micheel is a consultant at Roche and reports receiving a commercial research grant from GenomOncology. S.M. Sweeney is director of the AACR Project GENIE Coordinating Center at the AACR and reports receiving commercial research grants from Amgen, Inc., Analysis Group, Novartis, AstraZeneca UK Limited, Bayer Healthcare Pharmaceuticals, Inc., Boehringer Ingelheim, Bristol-Myers Squibb Company, Genentech, Janssen Pharmaceuticals, Inc., H3 Biomedicine, and Merck Sharp & Dohme Corp. J. Lee reports receiving commercial research grants from Amgen, Inc., Bristol-Myers Squibb Company, Janssen Pharmaceuticals, Inc., Analysis Group, Merck Sharp & Dohme Corp., AstraZeneca UK Limited, Genentech, Novartis, Bayer Healthcare Pharmaceuticals, Inc., H3 Biomedicine, Puma Biotechnology, and Boehringer Ingelheim. S. Sheffler-Collins is a project manager at the AACR and reports receiving commercial research grants from Amgen Inc., Bristol-Myers Squibb Company, Janssen Pharmaceuticals, Inc., Analysis Group, Merck Sharp & Dohme Corp., AstraZeneca UK Limited, Genentech, Novartis, Bayer Healthcare Pharmaceuticals, Inc., H3 Biomedicine, Puma Biotechnology, and Boehringer Ingelheim. B.H. Park is an SAB member/consultant for Loxo Oncology and Celcuity and a consultant for Jackson Laboratories, Casdin Capital, H3 Biomedicine, Roche, and AstraZeneca, reports receiving commercial research grants from Foundation Medicine, Pfizer, and AbbVie, has ownership interest (including patents) in Loxo Oncology and Celcuity, and is a consultant/advisory board member for Tempus. C.L. Sawyers is on the board of directors of Novartis, is a scientific advisory board member for Agios, Nextech, Foghorn, Arsenal, Beigene, Blueprint, KSQ, PMV, Oric, Petra, Housey, and Column Group, has ownership interest (including patents) as inventor of enzalutamide and apalutamide, and is a science trustee for Cold Spring Harbor Laboratories. F. André reports receiving commercial research grants (to institution) from AstraZeneca, Novartis, Pfizer, Lilly, and Roche. F. Meric-Bernstam is Chair at MD Anderson Cancer Center, reports receiving a commercial research grant from AstraZeneca, and has received honoraria from the speakers bureaus of Novartis and Genentech. P.L. Bedard reports
Funding Information:
This research was supported by the AACR Project GENIE Consortium and by AstraZeneca. Memorial Sloan Kettering Cancer Center authors are supported in part by the NIH/NCI Memorial Sloan Kettering Cancer Center Support Grant P30 CA008748. This work was supported in part by The Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy (F. Meric- Bernstam) and the Cancer Prevention and Research Institute of Texas (CPRIT) Precision Oncology Decision Support Core RP150535 (F. Meric-Bernstam).
Funding Information:
This research was supported by the AACR Project GENIE Consortium and by AstraZeneca. Memorial Sloan Kettering Cancer Center authors are supported in part by the NIH/NCI Memorial Sloan Kettering Cancer Center Support Grant P30 CA008748. This work was supported in part by The Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy (F. Meric-Bernstam) and the Cancer Prevention and Research Institute of Texas (CPRIT) Precision Oncology Decision Support Core RP150535 (F. Meric-Bernstam).
Funding Information:
receiving commercial research grants from AstraZeneca, Novartis, PTC Therapeutics, Signalchem Life Sciences, Servier, Sanofi, Lilly, BMS, GSK, Seattle Genetics, Pfizer, Merck, Genentech/Roche, Mersana, and Nektar and is a consultant/advisory board member for BMS and Sanofi. A. Iasonos is a consultant for Intellegenica and is a consultant/advisory board member for Mylan and Brightpath. D. Schrag is Editor of JAMA and has received honoraria from the speakers bureau of Pfizer. D.M. Hyman is a scientific advisory board member for Lilly and Fount and a consultant for Chugai, Boehringer Ingelheim, AstraZeneca, Pfizer, Bayer, and Genentech, and reports receiving commercial research grants from Bayer, AstraZeneca, and Puma Biotechnology. The AACR Project GENIE Consortium reports receiving commercial research grants from Amgen, Inc., Bristol-Myers Squibb Company, Merck Sharp & Dohme Corp., AstraZeneca UK Limited, Genentech, Novartis, H3 Biomedicine, Boehringer Ingelheim, Janssen Pharmaceuticals, Inc., and Analysis Group. No potential conflicts of interest were disclosed by the other authors.
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/4
Y1 - 2020/4
N2 - AKT inhibitors have promising activity in AKT1E17K -mutant estrogen receptor (ER)- positive metastatic breast cancer, but the natural history of this rare genomic subtype remains unknown. Utilizing AACR Project GENIE, an international clinicogenomic data-sharing consortium, we conducted a comparative analysis of clinical outcomes of patients with matched AKT1E17K -mutant (n = 153) and AKT1 -wild-type (n = 302) metastatic breast cancer. AKT1 -mutant cases had similar adjusted overall survival (OS) compared with AKT1 -wild-type controls (median OS, 24.1 vs. 29.9, respectively; P = 0.98). AKT1- mutant cases enjoyed longer durations on mTOR inhibitor therapy, an observation previously unrecognized in pivotal clinical trials due to the rarity of this alteration. Other baseline clinicopathologic features, as well as durations on other classes of therapy, were broadly similar. In summary, we demonstrate the feasibility of using a novel and publicly accessible clincogenomic registry to define outcomes in a rare genomically defined cancer subtype, an approach with broad applicability to precision oncology. SIGNIFICANCE: We delineate the natural history of a rare genomically distinct cancer, AKT1 E17K - mutant ER-positive breast cancer, using a publicly accessible registry of real-world patient data, thereby illustrating the potential to inform drug registration through synthetic control data.
AB - AKT inhibitors have promising activity in AKT1E17K -mutant estrogen receptor (ER)- positive metastatic breast cancer, but the natural history of this rare genomic subtype remains unknown. Utilizing AACR Project GENIE, an international clinicogenomic data-sharing consortium, we conducted a comparative analysis of clinical outcomes of patients with matched AKT1E17K -mutant (n = 153) and AKT1 -wild-type (n = 302) metastatic breast cancer. AKT1 -mutant cases had similar adjusted overall survival (OS) compared with AKT1 -wild-type controls (median OS, 24.1 vs. 29.9, respectively; P = 0.98). AKT1- mutant cases enjoyed longer durations on mTOR inhibitor therapy, an observation previously unrecognized in pivotal clinical trials due to the rarity of this alteration. Other baseline clinicopathologic features, as well as durations on other classes of therapy, were broadly similar. In summary, we demonstrate the feasibility of using a novel and publicly accessible clincogenomic registry to define outcomes in a rare genomically defined cancer subtype, an approach with broad applicability to precision oncology. SIGNIFICANCE: We delineate the natural history of a rare genomically distinct cancer, AKT1 E17K - mutant ER-positive breast cancer, using a publicly accessible registry of real-world patient data, thereby illustrating the potential to inform drug registration through synthetic control data.
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UR - http://www.scopus.com/inward/citedby.url?scp=85082780132&partnerID=8YFLogxK
U2 - 10.1158/2159-8290.CD-19-1209
DO - 10.1158/2159-8290.CD-19-1209
M3 - Article
C2 - 31924700
AN - SCOPUS:85082780132
SN - 2159-8274
VL - 10
SP - 526
EP - 535
JO - Cancer discovery
JF - Cancer discovery
IS - 4
ER -