- Adding taselisib to letrozole improved the objective response rate (ORR) in a phase 2 randomized trial of postmenopausal women with estrogen receptor (ER)-positive, HER2-negative early breast cancer.
Why this matters
- Taselisib is the second oral PI3K inhibitor under study for breast cancer; the first, alpelisib, was recently approved by the US Food and Drug Administration for metastatic breast cancer.
- Findings reported here are promising enough to warrant a phase 3 trial.
- Double-blind trial (n=334) conducted in 22 countries among 334 patients randomly assigned to 16 weeks of neoadjuvant letrozole (2.5 mg/day continuous) with placebo or oral taselisib (4 mg on a 5-days-on, 2-days-off schedule) for 16 weeks followed by surgery.
- Coprimary outcomes were ORR and pathologic complete response (pCR).
- Funding: Genentech; F. Hoffmann-La Roche.
- Median follow-up was 4.9 months.
- Taselisib-treated patients had a higher ORR, as assessed by MRI (50% vs 39%; OR=1.55, P=.049).
- The taselisib subgroup with PIK3CA mutations also showed greater response (56% vs 38%; OR=2.03, P=.033).
- No difference between groups in pCR across groups and across subsets with PIK3CA mutations.
- Most frequent grade 3-4 adverse events were gastrointestinal (8%), infections (5%), and skin-subcutaneous tissue disorders (5%).
- Not powered to detect relapse-free survival.