On September 18, the Food and Drug Administration approved a combination of two oral drugs, Inluriyo (imlunestrant) and Verzenio (abemaciclib), for certain adults with advanced breast cancer. Both are made by Eli Lilly. The approval applies to estrogen receptor (ER)-positive, HER2-negative cancers with an ESR1 mutation that have progressed after hormone therapy. Patients must have the mutation confirmed by an FDA-authorized test.
ESR1 mutations can develop during hormone therapy and make tumors resistant to treatment. A blood test that detects tumor DNA can identify the mutation. The combination pairs Inluriyo, which blocks and degrades estrogen receptors, with Verzenio, which inhibits proteins involved in cancer cell growth. Inluriyo was previously approved as a standalone treatment; Verzenio has been available since 2017.
The FDA based its decision on findings from EMBER-3, an Eli Lilly-funded trial involving 874 adults. In a subgroup of 159 participants whose tumors had ESR1 mutations, median progression-free survival was 11.1 months with the combination, compared with 5.5 months with Inluriyo alone. Tumors shrank in 35% and 15% of patients, respectively. The FDA cautioned that these subgroup findings did not address the trial’s primary research question. Whether the combination extends overall survival remains unknown.
Side effects require monitoring. In the trial, 86% of participants receiving both drugs developed diarrhea, including 9% with severe cases. About 6% discontinued treatment because of side effects. Safety warnings also include low white blood cell counts, liver problems, lung inflammation, blood clots and fetal harm. Prescribing information calls for regular blood counts and liver tests, particularly early in treatment.
The approval offers an option for people with advanced disease after hormone therapy stops working. Another approved drug, Etcamah (camizestrant), uses a different strategy: switching treatment when a blood test detects an ESR1 mutation, before scans show progression. Follow-up studies will assess its longer-term benefits.