- In this phase 2 NEO-ORB trial, adding the PI3K inhibitor alpelisib (vs placebo) to neoadjuvant endocrine therapy with letrozole fails to improve the objective response rate (ORR), regardless of PIK3CA-mutational status, in women with early hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.
Why this matters
- In patients with metastatic breast cancer in the phase 3 SOLAR-1 trial, the addition of alpelisib to letrozole extended PFS in patients with PIK3CA-mutant tumors.
- The NEO-ORB trial findings suggest that PI3K pathway alterations play a different role in early vs metastatic disease.
- NEO-ORB randomized, double-blind, placebo-controlled 24-week study (n=257) of alpelisib (300 mg/day)+letrozole (2.5 mg/day) was compared with placebo+letrozole in 2 groups of patients with T1c-T3 breast cancer: those with PIK3CA-mutations and those without (wild-type).
- Primary outcome was ORR and pathologic complete response (pCR) in PIK3CA-mutant and wild-type groups.
- Funding: Novartis Pharmaceuticals Corporation.
- No difference in ORR across groups, regardless of PIK3CA status (43% in the alpelisib group vs 45% in the placebo group in the PIK3CA-mutant group, and 63% vs 61% in the wild-type group).
- No differences in pCR, which was low across 4 groups.
- No differences in Ki-67 activity across 4 groups.
48% discontinuation rate with alpelisib+letrozole.