Add-on alpelisib not enough to improve response in HR+ early breast cancer
Adding alpelisib to 24-week neoadjuvant letrozole treatment fails to improve response in patients with HR-positive early breast cancer, according to the results of the phase II NEO-ORB trial.
NEO-ORB randomized 257 postmenopausal women to receive 2.5 mg/day letrozole with either 300 mg/day alpelisib (n=131) or placebo (n=126) for 24 weeks. All women had HR-positive, HER2-negative and T1c–T3 breast cancer. They were grouped according to PIK3CA mutational status.
Patients with PIK3CA mutations in the alpelisib vs placebo arm were older (median, 65.5 vs 61.0 years), more likely to have lymph node involvement (N1 or higher; 35 percent vs 27 percent) and T3-stage tumours (12 percent vs 0 percent).
The trial did not meet its primary objective of improved objective response (ORR) and pathologic complete response (pCR) rates with alpelisib. ORRs vs placebo were 43 percent vs 45 percent in the PIK3CA mutant cohort and 63 percent vs 61 percent in the PIK3CA wild-type cohort.
PCR rates were low in all groups. Reductions in Ki-67 were similar across treatment arms and cohorts.
In PIK3CA-mutant tumours, the addition of alpelisib yielded a greater decrease in phosphorylated AKT compared with placebo.
The present data suggest that alpelisib does not provide clinical benefit in the neoadjuvant setting, but considering the available clinical and experimental data in other indications, adding alpelisib to letrozole may still be an effective treatment strategy for HR+ advanced/metastatic breast cancer that harbours somatic alterations in the PI3K pathway, researchers said.