Disclosures: Martel reports honoraria from Novartis. Please see the study for all other researchers’ relevant financial disclosures.
March 11, 2021
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Weight loss linked to poorer survival outcomes in HER2-positive early breast cancer

Disclosures: Martel reports honoraria from Novartis. Please see the study for all other researchers’ relevant financial disclosures.
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Weight loss after diagnosis of HER2-positive early breast cancer appeared associated with poorer survival outcomes, according to study results published in Journal of the National Comprehensive Cancer Network.

“The finding that weight loss, not weight gain, was associated with worse outcomes is unexpected,” Samuel Martel, MD, researcher at University of Sherbrooke in Quebec, Canada, said in a press release. “We were unable to make a distinction between intentional vs. unintentional weight loss, so it is a matter of speculation whether worse outcomes were due to weight loss or vice versa.”

Impact of weight on survival outcomes.
Data derived from Martel S, et al. J Natl Comp Canc Netw. 2021;doi:10.6004/jnccn.2020.7606.

For the unplanned exploratory analysis of the randomized, phase 3 ALTTO BIG 2-06 trial, Martel and colleagues assessed the impact of BMI at baseline and changes in weight 2 years after HER2-positive early-stage breast cancer diagnosis on DFS, distant DFS and OS.

The analysis included 8,381 patients (69% white) in the trial who had been randomly assigned to one of four treatments, including trastuzumab (Herceptin, Genentech) alone (n = 2,097); lapatinib (Tykerb, Novartis) alone (n = 2,100); trastuzumab for 12 weeks followed by lapatinib for 34 weeks (n = 2,091); or trastuzumab plus lapatinib (n = 2,093).

Researchers grouped patients into four categories according to WHO BMI classification: underweight (< 18.5 kg/m²), normal weight (18.5 kg/m² to < 25 kg/m²), overweight ( 25 kg/m² to < 30 kg/m²) and obese ( 30 kg/m²).

Overall, 2.2% of patients were underweight at baseline, 45.3% were normal weight, 32.1% were overweight and 20.4% had obesity.

DFS, distant DFS and OS served as the study’s endpoints.

Median follow-up was 4.5 years.

Results showed patients deemed obese at baseline experienced worse distant DFS (adjusted HR [aHR] = 1.25; 95% CI, 1.04-1.5) and OS (aHR = 1.27; 95% CI, 1.01-1.6) than patients of normal weight. However, researchers observed no significant difference in DFS between patients who had obesity vs. those of normal weight (aHR = 1.14; 95% CI, 0.97-1.32).

Researchers additionally found that weight loss of 5% or more at 2 years after randomization was associated with worse DFS (aHR = 1.34; 95% CI, 1.05-1.71), distant DFS (aHR = 1.46; 95% CI, 1.07-1.98) and OS (aHR = 1.83; 95% CI, 1.18-2.84).

Conversely, weight gain of 5% or more at 2 years after randomization did not significantly affect DFS (aHR = 1.16; 95% CI, 0.96-1.4), distant DFS (aHR = 1.25; 95% CI, 0.99-1.59) or OS (aHR = 1.21; 95% CI, 0.82-1.77).

Menopausal and hormonal receptor status influenced outcomes, but not anti-HER2 treatment type, according to researchers.

Of the patients who had obesity at baseline and experienced weight loss, researchers observed significantly worse OS (adjusted HR = 3.01; 95% CI, 1.38-6.57) and a higher incidence of grade 3 and grade 4 adverse events (P < .001), as well as adverse events that led to treatment discontinuation (P < .001).

“Is our general advice to [patients with obesity or overweight] to exercise and lose weight wrong?” Anthony D. Elias, MD, professor of medicine and medical oncology at University of Colorado Anschutz Medical Campus and member of the NCCN Clinical Practice Guidelines Panel for Breast Cancer, who was not involved with the study, said in the release. “Careful examination of the Kaplan-Meier hazard plots suggests that the relapse curves for those with weight loss are steeper in the second and third years of follow-up, but thereafter are relatively parallel. It’s possible that the weight loss observed early may be an indication for impending relapse of breast cancer.”