Conventional Therapy Outshines Everolimus for Breast Cancer With Certain Mutations

In In The News by Barbara Jacoby

By: Kaitlyn Manasterski

From: oncnet.com

Everolimus may not be effective for patients with breast cancer and PI3K/AKT/mTOR pathway mutations, according to a recent retrospective cohort study comparing the efficacy of everolimus with conventional therapy in patients with refractory breast cancer and mutations activating the PI3K/AKT/mTOR pathways (Cancer Med. 2019 Aug 6. Epub ahead of print).

 

“Previous case reports have shown the promising antitumor activity of everolimus in solid tumors containing molecular aberrations in PI3K/ATK/mTOR [sic] pathway, however, whether it is effective in patients with breast cancer remains unknown,” Zhanhong Chen, MS, Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China, and colleagues said.

 

Between September 2015 and October 2017, a total of 78 patients were screened at 2 sites; 52 patients were determined to have at least 1 gene mutation in PI3K/AKT/mTOR pathway and were included in the study, with PIK3CA being the most common mutation observed. Ultimately, 32 patients were eligible for efficacy analysis, including 19 in the everolimus arm of the trial, and 13 in the conventional therapy arm.

The main end point of the study was progression-free survival (PFS); secondary end points were overall response rate (ORR), disease control rate (DCR), and safety profile. The median follow-up period was 11 months.

 

The everolimus arm exhibited shorter PFS than did the conventional therapy arm, with a median of 1.9 versus 6.1 months, respectively (hazard ratio, 3.6; 95% CI, 1.48‐8.81; P = .0005). The everolimus arm’s ORR was 15.4% versus 23.1% in the conventional therapy arm, and DCR was 30.8% versus 100% respectively.

 

Of note, grade 3-5 adverse events occurred at a relatively higher rate in the conventional therapy arm versus the everolimus arm (38.5% vs 26.3%, respectively).

 

“Our findings suggested that everolimus might not be effective for cancer patients harboring mutations in PI3K/ATK/mTOR [sic] pathway and physicians should be cautious about its off‐label use in clinical practice,” concluded Mr Chen and colleagues.

 

“Future studies in a larger cohort is warranted for further exploration of the efficacy of genotype‐directed treatment,” they added.