Lindsey M Charo1,2, Ramez N Eskander1,2, Jason Sicklick1,3, Ki Hwan Kim4, Hyo Jeong Lim5, Ryosuke Okamura1, Suzanna Lee1, Rupa Subramanian1, Richard Schwab1, Rebecca Shatsky1, Steven Plaxe2, Shumei Kato1, Razelle Kurzrock1. 1. Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego Moores Cancer Center, La Jolla, CA. 2. Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Diego Moores Cancer Center, La Jolla, CA. 3. Division of Surgical Oncology, Department of Surgery, UC San Diego Moores Cancer Center, San Diego, CA. 4. Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, South Korea. 5. Department of Internal Medicine, Veterans Health Service Medical Center, Seoul, South Korea.
Abstract
PURPOSE: Next-generation sequencing is increasingly used in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide matched therapy; however, outcome data are limited. We evaluate the effect of the degree of matching of tumors to treatment as well as compliance to MTB recommendations on outcomes. METHODS: Overall, 164 patients with consecutive gynecologic and breast cancers presented at MTB were assessed for clinicopathologic data, next-generation sequencing results, MTB recommendations, therapy received, and outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment over total pathogenic alterations, and compliance to MTB recommendations were analyzed in context of oncologic outcomes. RESULTS: Altogether, 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS ≥ 40% had higher overall response rate (30.8% v 7.1%; P = .001), progression-free survival (PFS; hazard ratio [HR] 0.51; 95% CI, 0.31 to 0.85; P = .002), and a trend toward improved overall survival (HR 0.64; 95% CI, 0.34 to 1.25; P = .082) in univariate analysis. The PFS advantage remained significant in multivariate analysis (HR 0.5; 95% CI, 0.3 to 0.8; P = .006). Higher MTB recommendation compliance was significantly associated with improved median PFS (9.0 months for complete; 6.0 months for partial; 4.0 months for no compliance; P = .004) and overall survival (17.1 months complete; 17.8 months partial; 10.8 months none; P = .046). Completely MTB-compliant patients had higher MS (P < .001). In multivariate analysis comparing all versus none MTB compliance, overall response (HR 9.5; 95% CI, 2.6 to 35.0; P = .001) and clinical benefit (HR 8.8; 95% CI, 2.4 to 33.2; P = .001) rates were significantly improved with higher compliance. CONCLUSION: Compliance to MTB recommendations resulted in higher degrees of matched therapy and correlates with improved outcomes in patients with gynecologic and breast cancers.
PURPOSE: Next-generation sequencing is increasingly used in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide matched therapy; however, outcome data are limited. We evaluate the effect of the degree of matching of tumors to treatment as well as compliance to MTB recommendations on outcomes. METHODS: Overall, 164 patients with consecutive gynecologic and breast cancers presented at MTB were assessed for clinicopathologic data, next-generation sequencing results, MTB recommendations, therapy received, and outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment over total pathogenic alterations, and compliance to MTB recommendations were analyzed in context of oncologic outcomes. RESULTS: Altogether, 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS ≥ 40% had higher overall response rate (30.8% v 7.1%; P = .001), progression-free survival (PFS; hazard ratio [HR] 0.51; 95% CI, 0.31 to 0.85; P = .002), and a trend toward improved overall survival (HR 0.64; 95% CI, 0.34 to 1.25; P = .082) in univariate analysis. The PFS advantage remained significant in multivariate analysis (HR 0.5; 95% CI, 0.3 to 0.8; P = .006). Higher MTB recommendation compliance was significantly associated with improved median PFS (9.0 months for complete; 6.0 months for partial; 4.0 months for no compliance; P = .004) and overall survival (17.1 months complete; 17.8 months partial; 10.8 months none; P = .046). Completely MTB-compliant patients had higher MS (P < .001). In multivariate analysis comparing all versus none MTB compliance, overall response (HR 9.5; 95% CI, 2.6 to 35.0; P = .001) and clinical benefit (HR 8.8; 95% CI, 2.4 to 33.2; P = .001) rates were significantly improved with higher compliance. CONCLUSION: Compliance to MTB recommendations resulted in higher degrees of matched therapy and correlates with improved outcomes in patients with gynecologic and breast cancers.
Authors: Ashton C Berger; Anil Korkut; Rupa S Kanchi; Apurva M Hegde; Walter Lenoir; Wenbin Liu; Yuexin Liu; Huihui Fan; Hui Shen; Visweswaran Ravikumar; Arvind Rao; Andre Schultz; Xubin Li; Pavel Sumazin; Cecilia Williams; Pieter Mestdagh; Preethi H Gunaratne; Christina Yau; Reanne Bowlby; A Gordon Robertson; Daniel G Tiezzi; Chen Wang; Andrew D Cherniack; Andrew K Godwin; Nicole M Kuderer; Janet S Rader; Rosemary E Zuna; Anil K Sood; Alexander J Lazar; Akinyemi I Ojesina; Clement Adebamowo; Sally N Adebamowo; Keith A Baggerly; Ting-Wen Chen; Hua-Sheng Chiu; Steve Lefever; Liang Liu; Karen MacKenzie; Sandra Orsulic; Jason Roszik; Carl Simon Shelley; Qianqian Song; Christopher P Vellano; Nicolas Wentzensen; John N Weinstein; Gordon B Mills; Douglas A Levine; Rehan Akbani Journal: Cancer Cell Date: 2018-04-02 Impact factor: 31.743
Authors: Lorna Rodriguez-Rodriguez; Kim M Hirshfield; Veronica Rojas; Robert S DiPaola; Darlene Gibbon; Mira Hellmann; Sara Isani; Aliza Leiser; Gregory M Riedlinger; Allison Wagreich; Siraj M Ali; Julia A Elvin; Vincent A Miller; Shridar Ganesan Journal: Gynecol Oncol Date: 2016-04 Impact factor: 5.482
Authors: Maria Schwaederle; Barbara A Parker; Richard B Schwab; Paul T Fanta; Sarah G Boles; Gregory A Daniels; Lyudmila A Bazhenova; Rupa Subramanian; Alice C Coutinho; Haydee Ojeda-Fournier; Brian Datnow; Nicholas J Webster; Scott M Lippman; Razelle Kurzrock Journal: Oncologist Date: 2014-05-05
Authors: Jordi Rodon; Jean-Charles Soria; Raanan Berger; Wilson H Miller; Eitan Rubin; Aleksandra Kugel; Apostolia Tsimberidou; Pierre Saintigny; Aliza Ackerstein; Irene Braña; Yohann Loriot; Mohammad Afshar; Vincent Miller; Fanny Wunder; Catherine Bresson; Jean-François Martini; Jacques Raynaud; John Mendelsohn; Gerald Batist; Amir Onn; Josep Tabernero; Richard L Schilsky; Vladimir Lazar; J Jack Lee; Razelle Kurzrock Journal: Nat Med Date: 2019-04-22 Impact factor: 53.440
Authors: Mansoor R Mirza; Bradley J Monk; Jørn Herrstedt; Amit M Oza; Sven Mahner; Andrés Redondo; Michel Fabbro; Jonathan A Ledermann; Domenica Lorusso; Ignace Vergote; Noa E Ben-Baruch; Christian Marth; Radosław Mądry; René D Christensen; Jonathan S Berek; Anne Dørum; Anna V Tinker; Andreas du Bois; Antonio González-Martín; Philippe Follana; Benedict Benigno; Per Rosenberg; Lucy Gilbert; Bobbie J Rimel; Joseph Buscema; John P Balser; Shefali Agarwal; Ursula A Matulonis Journal: N Engl J Med Date: 2016-10-07 Impact factor: 91.245
Authors: Jonathan A Ledermann; Philipp Harter; Charlie Gourley; Michael Friedlander; Ignace Vergote; Gordon Rustin; Clare Scott; Werner Meier; Ronnie Shapira-Frommer; Tamar Safra; Daniela Matei; Anitra Fielding; Stuart Spencer; Philip Rowe; Elizabeth Lowe; Darren Hodgson; Mika A Sovak; Ursula Matulonis Journal: Lancet Oncol Date: 2016-09-09 Impact factor: 41.316
Authors: David Allan Moore; Marina Kushnir; Gabriel Mak; Helen Winter; Teresa Curiel; Mark Voskoboynik; Michele Moschetta; Nataliya Rozumna-Martynyuk; Kevin Balbi; Philip Bennett; Martin Forster; Anjana Kulkarni; Debra Haynes; Charles Swanton; Hendrik-Tobias Arkenau Journal: ESMO Open Date: 2019-03-21
Authors: Lindsey M Charo; Ramez N Eskander; Ryosuke Okamura; Sandip P Patel; Mina Nikanjam; Richard B Lanman; David E Piccioni; Shumei Kato; Michael T McHale; Razelle Kurzrock Journal: Mol Oncol Date: 2020-09-17 Impact factor: 6.603