A randomized phase II trial of everolimus and letrozole or hormonal therapy in women with advanced, persistent or recurrent endometrial carcinoma: A GOG Foundation study.

Abstract

BACKGROUND:

Blocking the PI3K/AKT/mTOR pathway decreases resistance to hormonal therapy in endometrial carcinoma (EC).

OBJECTIVE:

In this study, the aim was to assess the efficacy and tolerability of everolimus(E)/letrozole (L) or medroxyprogesterone acetate(M)/tamoxifen(T) in the treatment of metastatic EC.

STUDY DESIGN:

This single stage, open-label two arm randomized phase II trial accrued women with advanced/persistent/recurrent EC. Treatment with E (10 mg daily) and L (2.5 mg daily) or T (20 mg twice daily) and M (200 mg daily alternating weeks) was randomly assigned, and stratified by prior adjuvant therapy. Treatments were administered orally. Primary endpoint was response rate.

RESULTS:

Between February 2015 and April 2016, everolimus/letrozole (n = 37) or MT (n = 37) was assigned to 74 patients. Median follow-up was 37 months. Eight (22%; 95% CI 11% to 37%) patients responded on EL (one CR) and nine (25%; 95% CI 14% to 41%) patients responded on MT (three CRs). Median PFS for EL and MT arms was 6 months and 4 months, respectively. On EL, chemo-nave patients demonstrated a 28 month median PFS; prior chemotherapy patients had a 4-month median PFS. On MT, patients without prior therapy had a 5-month median PFS; those with prior chemotherapy demonstrated a 3-month PFS. Common grade 3 adverse events were anemia (9 [24%] patients EL vs 2 [6%] MT) and mucositis (2 [5%] vs 0 [0%]). Grade 3/4 thromboembolic events were observed with MT but not with EL (0 [0%] vs 4 [11%]).

CONCLUSIONS:

EL and MT demonstrated clinically meaningful efficacy in recurrent EC patients. The higher PFS observed in chemo-naïve patients is worthy of confirmation in future studies.

• Authors: Brian M Slomovitz, Virginia L Filiaci, Joan L Walker, Michael C Taub, Karen A Finkelstein, John W Moroney, Aimee C Fleury, Carolyn Y Muller, Laura L Holman, Larry J Copeland, David S Miller, Robert L Coleman
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 164 Issue 3 Pg. 481-491 (03 2022) ISSN: 1095-6859 [Electronic] United States
• PMID: 35063278 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Drug Combinations
• Estrone
• Estradiol
• hormonin
• Letrozole
• Everolimus
• Estriol

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Drug Combinations
• Endometrial Neoplasms (drug therapy, pathology)
• Estradiol
• Estriol
• Estrone
• Everolimus (therapeutic use)
• Female
• Humans
• Letrozole (therapeutic use)
• Neoplasm Recurrence, Local (drug therapy, pathology)
• Phosphatidylinositol 3-Kinases