Clinical Study

Quality of life under extended continuous versus intermittent adjuvant letrozole in lymph node-positive, early breast cancer patients: the SOLE randomised phase 3 trial

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Abstract

Background

In the phase III SOLE trial, the extended use of intermittent versus continuous letrozole for 5 years did not improve disease-free survival in postmenopausal women with hormone receptor-positive breast cancer. Intermittent therapy with 3-month breaks may be beneficial for patients’ quality of life (QoL).

Methods

In the SOLE QoL sub-study, 956 patients completed the Breast Cancer Prevention Trial (BCPT) symptom and further QoL scales up to 24 months after randomisation. Differences in change of QoL from baseline between the two administration schedules were tested at 12 and 24 months using repeated measures mixed-models. The primary outcome was change in hot flushes at 12 months.

Results

There was no difference in hot flushes at 12 months between the two schedules, but patients receiving intermittent letrozole reported significantly more improvement at 24 months. They also indicated less worsening in vaginal problems, musculoskeletal pain, sleep disturbance, physical well-being and mood at 12 months. Overall, 25–30% of patients reported a clinically relevant worsening in key symptoms and global QoL.

Conclusion

Less symptom worsening was observed during the first year of extended treatment with the intermittent administration. For women experiencing an increased symptom burden of extended adjuvant endocrine therapy, an intermittent administration is a safe alternative.

Clinical trial information

Clinical trial information: NCT00651456.

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Acknowledgements

SOLE is a Breast International Group trial (BIG 01-07). We thank the patients, physicians, nurses, and trial coordinators who participated in the SOLE quality of life sub-study. SOLE receives financial support for trial conduct from Novartis and the International Breast Cancer Study Group (IBCSG). Novartis provided the letrozole used in this study. Support for the coordinating group, IBCSG, was provided by the Frontier Science & Technology Research Foundation; the Swiss Group for Clinical Cancer Research; Cancer Research Switzerland, Oncosuisse and the Cancer League Switzerland; and the Foundation for Clinical Cancer Research of Eastern Switzerland.

Author contributions

Conception and design: Karin Ribi, Weixiu Luo, Marco Colleoni, Per Karlsson, Jacquie Chirgwin, Stefan Aebi, Richard D. Gelber, Aron Goldhirsch, Alan S. Coates, Meredith M. Regan, Jürg Bernhard. Collection and assembly of data: Marco Colleoni, Per Karlsson, Jacquie Chirgwin, Stefan Aebi, Guy Jerusalem, Patrick Neven, Vincenzo Di Lauro, Henry L. Gomez, Thomas Ruhstaller, Ehtesham Abdi, Laura Biganzoli, Bettina Müller, Annelore Barbeaux, Marie-Pascale Graas, Manuela Rabaglio, Prudence A. Francis, Theodoros Foukakis, Olivia Pagani, Claudio Graiff, Daniel Vorobiof, Angelo Di Leo, Meredith M. Regan. Provision of study materials or patients: Marco Colleoni, Per Karlsson, Jacquie Chirgwin, Stefan Aebi, Guy Jerusalem, Patrick Neven, Vincenzo Di Lauro, Henry L. Gomez, Thomas Ruhstaller, Ehtesham Abdi, Laura Biganzoli, Bettina Müller, Annelore Barbeaux, Marie-Pascale Graas, Manuela Rabaglio, Prudence A. Francis, Theodoros Foukakis, Olivia Pagani, Claudio Graiff, Daniel Vorobiof, Angelo Di Leo, Meredith M. Regan. Data analysis and interpretation: Karin Ribi, Weixiu Luo, Alan S. Coates, Richard D. Gelber, Meredith M. Regan, Jürg Bernhard. Manuscript writing: All authors. Final approval of manuscript: All authors

Author information

Correspondence to Jürg Bernhard.

Ethics declarations

Competing interests

Dr Colleoni reports advisory board fees from AstraZeneca, Pierre Fabre, Pfizer, OBI Pharma, Puma Biotechnology, Celldex; and honoraria from Novartis. Dr Karlsson reports advisory board fees from Novartis. Dr Jerusalem reports grants from Novartis, Roche, Amgen, BMS, and MSD; personal fees from Novartis, Roche, Lilly, Celgene, Amgen, BMS, Pfizer, Puma, Daiichi-Sankyo, MSD, and AstraZeneca; and non-financial support from Novartis, Roche, Lilly, BMS, and AstraZeneca. Dr Ruhstaller reports travel grants from Roche and Amgen; and advisory board fees from Novartis, Roche, AstraZeneca, and Lilly; and honoraria from Pfizer. Dr Francis reports personal fees from AstraZeneca and Novartis; and non-financial support from Pfizer: Dr Foukakis reports an institutional grant from Pfizer; and personal fees from Novartis and UpToDate. Dr Leo reports grants from AstraZeneca, Pierre Fabre, and Pfizer; and personal fees from AstraZeneca, Bayer, Celgene, Daichii-Sankyo, Eisai, Genomic Health, Ipsen, Lilly, Novartis, Pierre Fabre, Pfizer, and Roche. Dr Gelber reports institution fees from Novartis, Pfizer, AstraZeneca, Merck, Celgene, Ferring, Roche, and Ipsen. Dr Goldhirsch reports that the institute received a per-patient fee from the IBCSG for trial conduct. Dr Regan reports grants from International Breast Cancer Study Group, during the conduct of the study; grants from Novartis, grants from Pfizer, grants from Ipsen, outside the submitted work. The remaining authors declare no competing interests.

Ethics approval

Ethics committees and appropriate national health authorities from each centre approved the protocol, including this sub-study, and all patients provided written informed consent as part of the informed consent for the main trial. The study was performed in accordance with the Declaration of Helsinki.

Data availability

The data on which these analyses are based forms part of the clinical trials database of the International Breast Cancer Study Group, and as such is available for use on application in accordance with IBCSG data sharing policy.

Note

This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

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Presented: 2017 San Antonio Breast Cancer Symposium, San Antonio, TX, USA.

The investigators in the Study of Letrozole Extension (SOLE), the leadership and staff of the International Breast Cancer Study Group, and the trial’s support and acknowledgments are listed in the Supplementary Appendix.

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Ribi, K., Luo, W., Colleoni, M. et al. Quality of life under extended continuous versus intermittent adjuvant letrozole in lymph node-positive, early breast cancer patients: the SOLE randomised phase 3 trial. Br J Cancer 120, 959–967 (2019) doi:10.1038/s41416-019-0435-4

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