March 22, 2022
2 min learn
Konstantinopoulos PA, et al. Part 2, two-stage examine of letrozole and abemaciclib in estrogen receptor (ER) optimistic recurrent or persistent endometrial most cancers. Introduced at: Society of Gynecologic Oncology Annual Assembly on Girls’s Most cancers; March 18-21, 2022; Phoenix (hybrid assembly).
Disclosures: Konstantinopoulos experiences consulting for Alkermes, AstraZeneca, BMS, GSK, Kadmon, Repare Therapeutics and Shattuck Labs. Please see the total examine for all others authors’ related monetary disclosures.
Outcomes from a part 2 examine confirmed that abemaciclib together with letrozole shrunk or stabilized tumors in 75% of sufferers with recurrent or persistent estrogen receptor-positive, or ER-positive, endometrial most cancers.
“For sufferers with ER-positive endometrial most cancers, hormonal/endocrine remedy is used as a substitute possibility after development by means of chemotherapy and immunotherapy or as a substitute, much less poisonous possibility for these with extra indolent or minimally symptomatic illness,” Panagiotis A. Konstantinopoulos, MD, PhD, director of gynecologic oncology translational analysis and doctor at Dana-Farber Most cancers Institute, advised Healio. “Nevertheless, responses to endocrine remedy are usually modest and comparatively temporary in length (median progression-free survival of about 3 months), with solely a minority of sufferers deriving profit for prolonged time frame.
“In prior research, aromatase inhibitor monotherapy displays restricted exercise in endometrial most cancers, with response charges for each letrozole and anastrozole beneath 10%,” Konstantinopoulos, additionally an affiliate professor of drugs at Harvard Medical College, stated. “For that reason, growth of novel methods to enhance the efficacy of endocrine remedy represents an unmet want and an space of energetic investigation in endometrial most cancers.”
Within the examine, introduced on the Society of Gynecologic Oncology Annual Assembly on Girls’s Most cancers, the researchers evaluated the efficacy of 150 mg of abemaciclib twice day by day and a pair of.5 mg of letrozole day by day — a focused drug and an aromatase inhibitor, respectively — in 28 sufferers who had recurrent ER-positive endometrial cancer, based on the summary. They analyzed the target response fee and the progression-free survival fee at 6 months.
At a median follow-up of 12.5 months, 75% of sufferers’ tumors had develop into smaller or stabilized, and about 30% had their tumors shrink by not less than 30%, based on a press launch from the Dana-Farber Most cancers Institute.
Development-free survival at 6 months was 55.6% (95% CI, 35.1%-72%), with a median progression-free survival of 9.1 months (95% CI, 3.5-16.5).
The most typical toxicities have been neutropenia in 5 sufferers and anemia in three sufferers; two sufferers discontinued therapy because of toxicity. There was not less than one dose discount of abemaciclib in 16 sufferers.
“Letrozole/abemaciclib demonstrated encouraging and sturdy proof of exercise in recurrent ER-positive endometrial most cancers and should an efficient endocrine remedy strategy for sufferers with recurrent ER-positive endometrioid endometrial most cancers,” Konstantinopoulos advised Healio.
Shifting ahead, the researchers will study genomic mutations associated to endocrine resistance.
“Extra deliberate future correlative work from our examine contains assessing genomic alterations related to endocrine resistance (resembling ESR1 and PIK3CA mutations) on circulating tumor DNA from serial blood specimens collected from sufferers at baseline (previous to initiation of protocol remedy), at C2D1, on the time of response and on the time of development,” Konstantinopoulos stated.