AKT Inhibition in Solid Tumors With AKT1 Mutations.

Autor: Hyman DM; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Smyth LM; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Donoghue MTA; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Westin SN; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Bedard PL; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Dean EJ; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Bando H; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., El-Khoueiry AB; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Pérez-Fidalgo JA; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Mita A; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Schellens JHM; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Chang MT; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Reichel JB; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Bouvier N; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Selcuklu SD; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Soumerai TE; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Torrisi J; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Erinjeri JP; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Ambrose H; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Barrett JC; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Dougherty B; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Foxley A; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Lindemann JPO; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., McEwen R; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Pass M; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Schiavon G; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Berger MF; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Chandarlapaty S; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Solit DB; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Banerji U; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Baselga J; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands., Taylor BS; David M. Hyman, Lillian M. Smyth, Mark T.A. Donoghue, Matthew T. Chang, Jonathan B. Reichel, Nancy Bouvier, S. Duygu Selcuklu, Tara E. Soumerai, Jean Torrisi, Joseph P. Erinjeri, Michael F. Berger, Sarat Chandarlapaty, David B. Solit, José Baselga, and Barry S. Taylor, Memorial Sloan Kettering Cancer Center; David B. Solit, Weill Cornell Medical College, Cornell University, New York, NY; J. Carl Barrett and Brian Dougherty, AstraZeneca, Waltham, MA; Helen Ambrose, Andrew Foxley, Justin P.O. Lindemann, Robert McEwen, Martin Pass, and Gaia Schiavon, AstraZeneca, Cambridge; Emma J. Dean, The Christie National Health Service Foundation, Manchester; Udai Banerji, Royal Marsden Hospital, London, United Kingdom; Shannon N. Westin, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe L. Bedard, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hideaki Bando, National Cancer Center East Hospital, Kashiwa, Japan; Anthony B. El-Khoueiry, University of Southern California Norris Comprehensive Cancer Center; Alain Mita, Cedars-Sinai Medical Center, Los Angeles, CA; José A. Pérez-Fidalgo, Hospital Clinico de Valencia, Valencia, Spain; and Jan H.M. Schellens, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Jazyk: angličtina
Zdroj: Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2017 Jul 10; Vol. 35 (20), pp. 2251-2259. Date of Electronic Publication: 2017 May 10.
DOI: 10.1200/JCO.2017.73.0143
Abstrakt: Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary activity of AKT inhibition in AKT-mutant cancers. Patients and Methods Fifty-eight patients with advanced solid tumors were treated. The primary end point was safety; secondary end points were progression-free survival (PFS) and response according to Response Evaluation Criteria in Solid Tumors (RECIST). Tumor biopsies and plasma cell-free DNA (cfDNA) were collected in the majority of patients to identify predictive biomarkers of response. Results In patients with AKT1 E17K-mutant tumors (n = 52) and a median of five lines of prior therapy, the median PFS was 5.5 months (95% CI, 2.9 to 6.9 months), 6.6 months (95% CI, 1.5 to 8.3 months), and 4.2 months (95% CI, 2.1 to 12.8 months) in patients with estrogen receptor-positive breast, gynecologic, and other solid tumors, respectively. In an exploratory biomarker analysis, imbalance of the AKT1 E17K-mutant allele, most frequently caused by copy-neutral loss-of-heterozygosity targeting the wild-type allele, was associated with longer PFS (hazard ratio [HR], 0.41; P = .04), as was the presence of coincident PI3K pathway hotspot mutations (HR, 0.21; P = .045). Persistent declines in AKT1 E17K in cfDNA were associated with improved PFS (HR, 0.18; P = .004) and response ( P = .025). Responses were not restricted to patients with detectable AKT1 E17K in pretreatment cfDNA. The most common grade ≥ 3 adverse events were hyperglycemia (24%), diarrhea (17%), and rash (15.5%). Conclusion This study provides the first clinical data that AKT1 E17K is a therapeutic target in human cancer. The genomic context of the AKT1 E17K mutation further conditioned response to AZD5363.
Databáze: MEDLINE