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

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.

Conflict of interest statement

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.

Figures

Fig. 1

CONSORT flowchart to identify the 955-patient intention-to-treat (ITT) quality of life population. QoL, quality of life

Fig. 2

Absolute scores (mean with 95% CI) from baseline to 24 months according to treatment assignment for BCPT symptom scales of hot flushes, vaginal problems, and musculoskeletal pain (score range 0–4; higher scores indicating a worse condition), and QoL LASA indicator for treatment burden (score range 0–100; higher score indicates better condition. CI, confidence interval; QoL, quality of life; BCPT, Breast Cancer Prevention Trial; LASA, linear analogue self-assessment

Fig. 3

Change of scores in BCPT symptom scales and symptom-specific and global QoL LASA scales from baseline to 12 and 24 months (mean with 95% CI), according to treatment assignment (BCPT symptom scales were recalculated to 0-100 range before calculating the change). CI, confidence interval; QoL, quality of life; BCPT, Breast Cancer Prevention Trial; LASA, linear analogue self-assessment

Fig. 4

Proportion of patients who reported clinically-relevant worsened, stable or improved scores for selected quality of life scales at 12 and 24 months according to treatment assignment