PURPOSE: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is), in combination with endocrine therapy (ET), are standard either in the first (1L) or second-line (2L) setting for the treatment of hormone receptor (HR) positive, HER2-negative metastatic breast cancer (MBC). However, the optimal sequencing of treatments after progression on CDK4/6i remains unknown. We performed a single-institution analysis to identify treatments and outcomes after progression on a CDK4/6i. METHODS: We identified patients with HR-positive, HER2-negative MBC prescribed a CDK4/6i in the 1L or 2L settings from December 2014 to February 2018 at Mayo Clinic in Rochester, Minnesota. Outcomes were collected through September 30, 2020. RESULTS: Palbociclib, in combination with letrozole or fulvestrant, was the most prescribed CDK4/6i. The 1L and 2L CDK4/6i cohorts exhibited comparable overall survival (OS), but progression-free survival (PFS) was longer in the 1L than the 2L cohort [28.2 months (95% CI 19.6-34.9) vs 19.8 months (95% CI 15.7-29.6)]. The most common post-CDK4/6i treatments were PI3K/mTOR inhibitors (PI3K/mTORi), single-agent ET, or chemotherapy. PFS in the 1L CDK4/6i cohort following PI3K/mTORi was 8.5 months (95% CI 5.5 months-NE), single-agent ET was 6.0 months (95% CI 3.3-14.0 months), and chemotherapy PFS was 5.4 months (95% CI 3.3 months-NE). CONCLUSIONS: Following progression on a CDK 4/6i, mPFS was short, with similar PFS times comparing chemotherapy and ET, with slightly longer PFS for targeted strategies (PI3K/mTOR). These results highlight a major need to better understand the mechanisms of CDK4/6i resistance and identify new therapeutic strategies for these patients.
PURPOSE: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is), in combination with endocrine therapy (ET), are standard either in the first (1L) or second-line (2L) setting for the treatment of hormone receptor (HR) positive, HER2-negative metastatic breast cancer (MBC). However, the optimal sequencing of treatments after progression on CDK4/6i remains unknown. We performed a single-institution analysis to identify treatments and outcomes after progression on a CDK4/6i. METHODS: We identified patients with HR-positive, HER2-negative MBC prescribed a CDK4/6i in the 1L or 2L settings from December 2014 to February 2018 at Mayo Clinic in Rochester, Minnesota. Outcomes were collected through September 30, 2020. RESULTS: Palbociclib, in combination with letrozole or fulvestrant, was the most prescribed CDK4/6i. The 1L and 2L CDK4/6i cohorts exhibited comparable overall survival (OS), but progression-free survival (PFS) was longer in the 1L than the 2L cohort [28.2 months (95% CI 19.6-34.9) vs 19.8 months (95% CI 15.7-29.6)]. The most common post-CDK4/6i treatments were PI3K/mTOR inhibitors (PI3K/mTORi), single-agent ET, or chemotherapy. PFS in the 1L CDK4/6i cohort following PI3K/mTORi was 8.5 months (95% CI 5.5 months-NE), single-agent ET was 6.0 months (95% CI 3.3-14.0 months), and chemotherapy PFS was 5.4 months (95% CI 3.3 months-NE). CONCLUSIONS: Following progression on a CDK 4/6i, mPFS was short, with similar PFS times comparing chemotherapy and ET, with slightly longer PFS for targeted strategies (PI3K/mTOR). These results highlight a major need to better understand the mechanisms of CDK4/6i resistance and identify new therapeutic strategies for these patients.
Authors: Richard S Finn; Miguel Martin; Hope S Rugo; Stephen Jones; Seock-Ah Im; Karen Gelmon; Nadia Harbeck; Oleg N Lipatov; Janice M Walshe; Stacy Moulder; Eric Gauthier; Dongrui R Lu; Sophia Randolph; Véronique Diéras; Dennis J Slamon Journal: N Engl J Med Date: 2016-11-17 Impact factor: 91.245
Authors: Dennis J Slamon; Patrick Neven; Stephen Chia; Peter A Fasching; Michelino De Laurentiis; Seock-Ah Im; Katarina Petrakova; Giulia V Bianchi; Francisco J Esteva; Miguel Martín; Arnd Nusch; Gabe S Sonke; Luis De la Cruz-Merino; J Thaddeus Beck; Xavier Pivot; Manu Sondhi; Yingbo Wang; Arunava Chakravartty; Karen Rodriguez-Lorenc; Tetiana Taran; Guy Jerusalem Journal: N Engl J Med Date: 2019-12-11 Impact factor: 91.245
Authors: Matthew P Goetz; Masakazu Toi; Mario Campone; Joohyuk Sohn; Shani Paluch-Shimon; Jens Huober; In Hae Park; Olivier Trédan; Shin-Cheh Chen; Luis Manso; Orit C Freedman; Georgina Garnica Jaliffe; Tammy Forrester; Martin Frenzel; Susana Barriga; Ian C Smith; Nawel Bourayou; Angelo Di Leo Journal: J Clin Oncol Date: 2017-10-02 Impact factor: 44.544
Authors: Gabriel N Hortobagyi; Salomon M Stemmer; Howard A Burris; Yoon-Sim Yap; Gabe S Sonke; Shani Paluch-Shimon; Mario Campone; Kimberly L Blackwell; Fabrice André; Eric P Winer; Wolfgang Janni; Sunil Verma; Pierfranco Conte; Carlos L Arteaga; David A Cameron; Katarina Petrakova; Lowell L Hart; Cristian Villanueva; Arlene Chan; Erik Jakobsen; Arnd Nusch; Olga Burdaeva; Eva-Maria Grischke; Emilio Alba; Erik Wist; Norbert Marschner; Anne M Favret; Denise Yardley; Thomas Bachelot; Ling-Ming Tseng; Sibel Blau; Fengjuan Xuan; Farida Souami; Michelle Miller; Caroline Germa; Samit Hirawat; Joyce O'Shaughnessy Journal: N Engl J Med Date: 2016-10-07 Impact factor: 91.245
Authors: Michael Gnant; Amylou C Dueck; Sophie Frantal; Miguel Martin; Hal J Burstein; Richard Greil; Peter Fox; Antonio C Wolff; Arlene Chan; Eric P Winer; Georg Pfeiler; Kathy D Miller; Marco Colleoni; Jennifer M Suga; Gabor Rubovsky; Judith M Bliss; Ingrid A Mayer; Christian F Singer; Zbigniew Nowecki; Olwen Hahn; Jacqui Thomson; Norman Wolmark; Kepa Amillano; Hope S Rugo; Guenther G Steger; Blanca Hernando Fernández de Aránguiz; Tufia C Haddad; Antonia Perelló; Meritxell Bellet; Hannes Fohler; Otto Metzger Filho; Anita Jallitsch-Halper; Kadine Solomon; Céline Schurmans; Kathy P Theall; Dongrui R Lu; Kathleen Tenner; Christian Fesl; Angela DeMichele; Erica L Mayer Journal: J Clin Oncol Date: 2021-12-07 Impact factor: 44.544