3-year invasive disease-free survival with chemotherapy de-escalation using an 18F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): a randomised, open-label, phase 2 trial.

Chen WY, Ballman KV, Partridge AH, Hahn OM, Briccetti FM et al.

JAMA 2024; 331: 1714-1721.

Some 3020 women with non-metastatic breast cancer were enrolled. The study was terminated after the first interim analysis for futility. 300mg aspirin per day for a median of 33.8 months did not improve breast cancer recurrence (hazard ratio 1.27, 95 per cent confidence interval 0.99 to 1.63, P=0.06) or survival (1.19, 0.82 to 1.72).

Comment: Theoretical advantage not proven.

Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF et al.
N Engl J Med 2021; 385: 2336-2347

The study included 5083 women with hormone receptor positive, HER 2 negative breast cancer with 1-3 positive axillary nodes and a recurrence score above 25. They all received endocrine therapy, and were randomized to additional chemotherapy. Five year overall survival rates were not improved with chemotherapy: 91.3 versus 91.9 percent, but disease-free survival was better in premenopausal women.

Comment: A large and complex trial that helps inform how to mange women with node positive breast cancer.

Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kummel S et al, for the KEYNOTE-522 Investigators.
N Engl J Med 2022; 386: 556-567.

Use of neoadjuvant pembrolizumab plus chemotherapy, with additional pembrolizumab postoperatively improved event-free survival from 76.8 to 84.5 per cent at 36 months in this study that included 1174 women.

Comment: New standard of care?