Targeting Androgen Receptor and DNA Repair in Metastatic Castration-Resistant Prostate Cancer: Results From NCI 9012.

Autor: Hussain M; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Daignault-Newton S; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Twardowski PW; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Albany C; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Stein MN; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Kunju LP; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Siddiqui J; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Wu YM; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Robinson D; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Lonigro RJ; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Cao X; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Tomlins SA; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Mehra R; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Cooney KA; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Montgomery B; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Antonarakis ES; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Shevrin DH; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Corn PG; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Whang YE; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Smith DC; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Caram MV; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Knudsen KE; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Stadler WM; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Feng FY; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA., Chinnaiyan AM; Maha Hussain, Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Walter M. Stadler, University of Chicago, Chicago; Daniel H. Shevrin, NorthShore University Health System, Evanston, IL; Maha Hussain, Stephanie Daignault-Newton, Lakshmi P. Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J. Lonigro, Xuhong Cao, Scott A. Tomlins, Rohit Mehra, David C. Smith, Megan V. Caram, and Arul M. Chinnaiyan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Przemyslaw W. Twardowski, City of Hope Cancer Center, Duarte; Felix Y. Feng, University of California San Francisco, San Francisco, CA; Costantine Albany, Simon Cancer Center, Indiana University, Indianapolis, IN; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Kathleen A. Cooney, University of Utah, Salt Lake City, UT; Bruce Montgomery, University of Washington, Seattle, WA; Emmanuel S. Antonarakis, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Paul G. Corn, University of Texas MD Anderson Cancer Center, Houston, TX; Young E. Whang, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Karen E. Knudsen, Thomas Jefferson University, Philadelphia, PA.
Jazyk: angličtina
Zdroj: Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2018 Apr 01; Vol. 36 (10), pp. 991-999. Date of Electronic Publication: 2017 Dec 20.
DOI: 10.1200/JCO.2017.75.7310
Abstrakt: Purpose To determine whether cotargeting poly (ADP-ribose) polymerase-1 plus androgen receptor is superior to androgen receptor inhibition in metastatic castration-resistant prostate cancer (mCRPC) and whether ETS fusions predict response. Patients and Methods Patients underwent metastatic site biopsy and were stratified by ETS status and randomly assigned to abiraterone plus prednisone without (arm A) or with veliparib (arm B). Primary objectives were: confirmed prostate-specific antigen (PSA) response rate (RR) and whether ETS fusions predicted response. Secondary objectives were: safety, measurable disease RR (mRR), progression-free survival (PFS), and molecular biomarker analysis. A total of 148 patients were randomly assigned to detect a 20% PSA RR improvement. Results A total of 148 patients with mCRPC were randomly assigned: arm A, n = 72; arm B, n = 76. There were no differences in PSA RR (63.9% v 72.4%; P = .27), mRR (45.0% v 52.2%; P = .51), or median PFS (10.1 v 11 months; P = .99). ETS fusions did not predict response. Exploratory analysis of tumor sequencing (80 patients) revealed: 41 patients (51%) were ETS positive, 20 (25%) had DNA-damage repair defect (DRD), 41 (51%) had AR amplification or copy gain, 34 (43%) had PTEN mutation, 33 (41%) had TP53 mutation, 39 (49%) had PIK3CA pathway activation, and 12 (15%) had WNT pathway alteration. Patients with DRD had significantly higher PSA RR (90% v 56.7%; P = .007) and mRR (87.5% v 38.6%; P = .001), PSA decline ≥ 90% (75% v 25%; P = .001), and longer median PFS (14.5 v 8.1 months; P = .025) versus those with wild-type tumors. Median PFS was longer in patients with normal PTEN (13.5 v 6.7 months; P = .02), TP53 (13.5 v 7.7 months; P = .01), and PIK3CA (13.8 v 8.3 months; P = .03) versus those with mutation or activation. In multivariable analysis adjusting for clinical covariates, DRD association with PFS remained significant. Conclusion Veliparib and ETS status did not affect response. Exploratory analysis identified a novel DRD association with mCRPC outcomes.
Databáze: MEDLINE