Monica Arnedos, MD, PhD, Head of the Breast Cancer Research Program at the Institut Bergonié, Bordeaux, France, commented on the study findings on extended treatment with letrozole. “We cannot ignore the results of the GIM4 trial.1 It provides additional strong evidence to support extended aromatase inhibitor therapy in postmenopausal patients, for a total duration of 7 to 8 years. This may be just enough, without needing to go to 10 years.”
A difference in invasive disease–free survival was shown in the intention-to-treat population, taking into account the events occurring since randomization. It was also shown in the post hoc landmark analysis, taking into account only those events occurring after treatment divergence, meaning that all events in the first 2 to 3 years were excluded, Dr. Arnedos said. An exploratory nonprespecified subgroup analysis indicated a benefit across all patients, and “very interestingly” the study also identified a significant overall survival benefit, she added.
Monica Arnedos, MD, PhD
Putting GIM4 Into Context
Dr. Arnedos said it is a bit difficult to put GIM4 into context with other phase III trials. The studies differ in the number of patients, length of extended endocrine therapy, time to randomization, previous endocrine therapy before randomization, and length of follow-up. Other studies have not been concordant in demonstrating a benefit from extended aromatase inhibitor treatment, which is why this practice is not strongly recommended in the main breast cancer guidelines, she explained.
“But now, we do have results from GIM4 that are positive, even in terms of overall survival. Does that mean tamoxifen for 2 to 3 years followed by 5 years of letrozole is the new standard of care?” Dr. Arnedos asked. “Would we have the same results if they had let some patients start with an aromatase inhibitor upfront? Or is the switching strategy one of the reasons for the positive results?” The answers to these questions are not clear.
The DATA trial2 was similar in design and could be the best comparator. This study failed to show a statistically significant improvement in disease-free survival for 6 years of anastrozole vs 3 years after tamoxifen (hazard ratio = 0.79; P = .066). However, it included more patients with node-positive disease, aimed for a 40% improvement, and had a median follow-up of just 4.2 years after treatment divergence. These factors “may be important, since low-risk patients tend to relapse late,” Dr. Arnedos said. “We would like to see the long-term follow-up data.”
Dr. Arnedos continued: “We also need to better define which patients may benefit from extended endocrine therapy beyond clinical characteristics, and we need to pay attention to the issues with compliance. It’s important to invest in programs that will support patients going through this treatment.”
DISCLOSURE: Dr. Arnedos has received honoraria from Novartis, AstraZeneca, and Pfizer; travel grants from Pfizer and Novartis; and research grants from Roche and AstraZeneca.
1. Del Mastro L, Mansutti M, Bisagni G, et al: Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: A randomised, phase III trial of the Gruppo Italiano Mammella. ESMO Congress 2021. Abstract 118O. Presented September 17, 2021.
2. Tjan-Heijnen VCG, van Hellemond IEG, Peer PGM, et al: Extended adjuvant aromatase inhibition after sequential endocrine therapy (DATA): A randomised, phase 3 trial. Lancet Oncol 18:1502-1511, 2017.
For patients with early-stage hormone receptor–positive breast cancer, extending the duration of letrozole after tamoxifen—for up to 8 years of total endocrine therapy—significantly improved invasive disease–free survival over the standard 5 or so years, according to the final analysis of the...