INTRODUCTION: Limited data exist on real-world treatment patterns and the effectiveness of cyclin-dependent kinase (CDK) 4/6 inhibitors in germline BRCA (gBRCA)-mutated breast cancer. METHODS: Adults with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) treated with CDK4/6 inhibitor therapy between 2013 and 2018 were retrospectively selected from the Flatiron Health database. Patients with known gBRCA status were classified as mutated (gBRCAm) or wild type (gBRCAwt). Time-to-first subsequent therapy or death (TFST) and overall survival (OS) were calculated from the earliest line of therapy with a CDK4/6 inhibitor. RESULTS: Of 2968 patients with HR+/HER2- mBC receiving a CDK4/6 inhibitor, 859 (28.9%) had known gBRCA status, of whom 9.9% were gBRCAm and 90.1% gBRCAwt. Median (95% confidence interval [CI]) TFST was 10 (7-11) months in the gBRCAm group, 10 (9-11) months in the gBRCAwt group, and 11 (10-12) months in the combined gBRCAwt and unknown gBRCA group; median (95% CI) OS was 26 (21-not estimated), 37 (31-51), and 33 (31-35) months, respectively. Cox models indicated the gBRCAm group had shorter TFST (stratified hazard ratio [sHR] 1.24; 95% CI 0.96-1.59) and OS (sHR 1.50; 95% CI 1.06-2.14) than the gBRCAwt group. The gBRCAm group had shorter TFST (sHR 1.38; 95% CI 1.08-1.75) and OS (sHR 1.22; 95% CI 0.88-1.71) than the combined group. CONCLUSION: The results of this real-world study suggest that treatment outcomes with CDK4/6 inhibitors may be worse in patients with gBRCAm mBC than in their counterparts with gBRCAwt and unknown gBRCA status, suggesting potential differences in tumor biology. This result highlights the unmet need in patients with gBRCAm requiring optimized treatment selection and sequencing. Future exploration in larger samples of patients who have had biomarker testing is warranted.
INTRODUCTION: Limited data exist on real-world treatment patterns and the effectiveness of cyclin-dependent kinase (CDK) 4/6 inhibitors in germline BRCA (gBRCA)-mutated breast cancer. METHODS: Adults with hormone receptor-positive (HR+), humanepidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) treated with CDK4/6 inhibitor therapy between 2013 and 2018 were retrospectively selected from the Flatiron Health database. Patients with known gBRCA status were classified as mutated (gBRCAm) or wild type (gBRCAwt). Time-to-first subsequent therapy or death (TFST) and overall survival (OS) were calculated from the earliest line of therapy with a CDK4/6 inhibitor. RESULTS: Of 2968 patients with HR+/HER2- mBC receiving a CDK4/6 inhibitor, 859 (28.9%) had known gBRCA status, of whom 9.9% were gBRCAm and 90.1% gBRCAwt. Median (95% confidence interval [CI]) TFST was 10 (7-11) months in the gBRCAm group, 10 (9-11) months in the gBRCAwt group, and 11 (10-12) months in the combined gBRCAwt and unknown gBRCA group; median (95% CI) OS was 26 (21-not estimated), 37 (31-51), and 33 (31-35) months, respectively. Cox models indicated the gBRCAm group had shorter TFST (stratified hazard ratio [sHR] 1.24; 95% CI 0.96-1.59) and OS (sHR 1.50; 95% CI 1.06-2.14) than the gBRCAwt group. The gBRCAm group had shorter TFST (sHR 1.38; 95% CI 1.08-1.75) and OS (sHR 1.22; 95% CI 0.88-1.71) than the combined group. CONCLUSION: The results of this real-world study suggest that treatment outcomes with CDK4/6 inhibitors may be worse in patients with gBRCAm mBC than in their counterparts with gBRCAwt and unknown gBRCA status, suggesting potential differences in tumor biology. This result highlights the unmet need in patients with gBRCAm requiring optimized treatment selection and sequencing. Future exploration in larger samples of patients who have had biomarker testing is warranted.
Authors: Jin Sun Lee; Susan E Yost; Sierra Min Li; Yujie Cui; Paul H Frankel; Yate-Ching Yuan; Daniel Schmolze; Colt A Egelston; Weihua Guo; Mireya Murga; Helen Chang; Linda Bosserman; Yuan Yuan Journal: Cancers (Basel) Date: 2022-06-28 Impact factor: 6.575
Authors: Robert S Miller; Stella Mokiou; Aliki Taylor; Ping Sun; Katherine Baria Journal: Breast Cancer Res Treat Date: 2022-02-22 Impact factor: 4.872
Authors: Volkmar Müller; Manfred Welslau; Diana Lüftner; Florian Schütz; Elmar Stickeler; Peter A Fasching; Wolfgang Janni; Christoph Thomssen; Isabell Witzel; Tanja N Fehm; Erik Belleville; Simon Bader; Katharina Seitz; Michael Untch; Marc Thill; Hans Tesch; Nina Ditsch; Michael P Lux; Bahriye Aktas; Maggie Banys-Paluchowski; Andreas Schneeweiss; Nadia Harbeck; Rachel Würstlein; Andreas D Hartkopf; Hans-Christian Kolberg; Achim Wöckel Journal: Geburtshilfe Frauenheilkd Date: 2022-06-03 Impact factor: 2.754
Authors: Tobias Engler; Peter A Fasching; Diana Lüftner; Andreas D Hartkopf; Volkmar Müller; Hans-Christian Kolberg; Peyman Hadji; Hans Tesch; Lothar Häberle; Johannes Ettl; Markus Wallwiener; Matthias W Beckmann; Alexander Hein; Erik Belleville; Sabrina Uhrig; Pauline Wimberger; Carsten Hielscher; Christian M Kurbacher; Rachel Wuerstlein; Michael Untch; Florin-Andrei Taran; Hans-Martin Enzinger; Petra Krabisch; Manfred Welslau; Michael Maasberg; Dirk Hempel; Michael P Lux; Laura L Michel; Wolfgang Janni; Diethelm Wallwiener; Sara Y Brucker; Tanja N Fehm; Andreas Schneeweiss Journal: Geburtshilfe Frauenheilkd Date: 2022-07-12 Impact factor: 2.754