Abstract
Purpose
Aromatase inhibitors (AI), which decrease circulating estradiol concentrations in post-menopausal women, are associated with toxicities that limit adherence. Approximately one-third of patients will tolerate a different AI after not tolerating the first. We report the effect of crossover from exemestane to letrozole or vice versa on patient-reported outcomes (PROs) and whether the success of crossover is due to lack of estrogen suppression.
Methods
Post-menopausal women enrolled on a prospective trial initiating AI therapy for early-stage breast cancer were randomized to exemestane or letrozole. Those that discontinued for intolerance were offered protocol-directed crossover to the other AI after a washout period. Changes in PROs, including pain [Visual Analog Scale (VAS)] and functional status [Health Assessment Questionnaire (HAQ)], were compared after 3 months on the first versus the second AI. Estradiol and drug concentrations were measured.
Results
Eighty-three patients participated in the crossover protocol, of whom 91.3% reported improvement in symptoms prior to starting the second AI. Functional status worsened less after 3 months with the second AI (HAQ mean change AI #1: 0.2 [SD 0.41] vs. AI #2: −0.05 [SD 0.36]; p = 0.001); change in pain scores was similar between the first and second AI (VAS mean change AI #1: 0.8 [SD 2.7] vs. AI #2: −0.2 [SD 2.8]; p = 0.19). No statistical differences in estradiol or drug concentrations were found between those that continued or discontinued AI after crossover.
Conclusions
Although all AIs act via the same mechanism, a subset of patients intolerant to one AI report improved PROs with a different one. The mechanism of this tolerance remains unknown, but does not appear to be due to non-adherence to, or insufficient estrogen suppression by, the second AI.
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Acknowledgements
This study was supported in part by U01-GM61373 and 5T32-GM08425 (DAF), M01-RR00042 (UM), M01-RR00750 (IU), and M01-RR00052 (JHU). NJS was supported (in part) by Cancer Center Biostatistics Training Grant 5T32-CA083654 (to J. Taylor). NLH was a Damon Runyon-Lilly Clinical Investigator supported (in part) by the Damon Runyon Cancer Research Foundation (Grant number CI-53-10) and by an American Cancer Society Research Scholar Grant. Additional support was provided by Fashion Footwear Association of New York/QVC Presents Shoes on Sale (DFH). In addition, the ELPh trial was supported by grants from Pfizer, Inc. and Novartis Pharma AG, who provided study medication.
Funding
Abbvie, Merck, Pfizer, MedImmune, Celgene, Puma Biotechnology, and Novartis (VS); Pfizer and Novartis (AMS); AstraZeneca, Janssen Research and Development, Puma Biotechnology, Pfizer, Eli Lilly Company (DFH); WellPoint and Genentech (CFS).
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Employment or Leadership Position: None, Consultant or Advisory Role: Walgreens and Pfizer (CFS); Pfizer (DFH), Stock Ownership: Immunomedics (CFS) Oncoimmune and InBiomotion (DFH), Honoraria: Pfizer (AMS); Lilly (DFH), All other authors had no conflicts of interest to disclose.
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David A. Flockhart was Deceased.
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10549_2017_4260_MOESM1_ESM.docx
Supplementary material 1 (DOCX 73 kb) Online Supplement 1—Diagram of the primary patient reported outcome analysis. PRO patient reported outcomes, AI aromatase inhibitor; Δ change
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Kadakia, K.C., Kidwell, K.M., Seewald, N.J. et al. Prospective assessment of patient-reported outcomes and estradiol and drug concentrations in patients experiencing toxicity from adjuvant aromatase inhibitors. Breast Cancer Res Treat 164, 411–419 (2017). https://doi.org/10.1007/s10549-017-4260-2
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DOI: https://doi.org/10.1007/s10549-017-4260-2