In the NCI-MATCH trial, which matches new treatments to patients with cancer based on the genetic makeup of their tumors, 22% of patients with AKT1 E17K–mutant metastatic tumors treated with the AKT inhibitor ipatasertib saw their tumors shrink, according to a novel study published by Kalinksy et al in the European Journal of Cancer. This included patients with breast and endometrial cancers, as well as rarer types of cancer such as anal and salivary gland cancers.
The research—also presented at the 34th European Organisation for Research and Treatment of Cancer (EORTC)–National Cancer Institute (NCI)–American Association for Cancer Research (AACR) Symposium on Molecular Targets and Cancer Therapeutics (Abstract 11)—involved a small number of patients with advanced cancers.
Research Background
Ipatasertib works by blocking the AKT protein, which helps cancer cells grow and spread after genetic changes in tumors.
“Although we have known about the role of AKT in cancer for decades, there are currently no AKT inhibitors that have approval from the U.S. Food and Drug Administration. Recently, several clinical trials have tested AKT inhibitors either alone or in combination with other treatments, with some success,” said Carolyn McCourt, MD, Associate Professor of Obstetrics and Gynecology in the Division of Gynecologic Oncology at the Siteman Cancer Center at the Washington University School of Medicine.
Research Methods and Results
In the study, patients all had tumors with the specific genetic alteration AKT1 E17K. This mutation is estimated to be present in up to 4% of breast tumors, 2% of endometrial tumors, and a small proportion of other solid tumors.
The majority of the 32 patients treated with ipatasertib in the study had already received at least three other types of treatments. During the trial, patients took ipatasertib orally once every day in 28-day cycles until disease progression or unacceptable toxicity.
In an estimated 44% of patients, tumors did not grow for at least 6 months while they were taking ipatasertib.
The most common side effects that patients experienced were diarrhea and nausea.
“This is a relatively small patient population, and we do not have a large number of each individual tumor type. However, we have found signs that this treatment could be working for some patients,” said Dr. McCourt. “We need to do more research to understand why some patients’ tumors did not respond to ipatasertib, while other patients experienced a prolonged time when their disease remained stable on this treatment. We also need to investigate whether we can combine ipatasertib with other drugs to improve the outcome for more patients,” she concluded.
The research team plans to analyze tumor samples further to look for any other clues that could help predict which patients will or will not benefit from taking this treatment.
“NCI-MATCH gives patients an opportunity to receive targeted therapies based on the genetic changes in their tumor[s], rather than where in the body their tumor[s] began to grow. It is an important trial because it involves patients with many different types of tumors. This includes particularly rare types of cancer, for which no standard treatments currently exist. It also offers alternative options for patients with cancers that have not responded to current recommended treatments,” said Ruth Plummer, MD, PhD, Professor of Experimental Cancer Medicine at Newcastle University and Chair of the 34th EORTC–NCI–AACR Symposium on Molecular Targets and Cancer Therapeutics, who was not involved in the study.
Disclosure: NCI-MATCH is co-led by the ECOG-ACRIN Cancer Research Group and the National Cancer Institute, part of the U.S. National Institutes of Health (NIH). For full disclosures of the study authors, visit ejcancer.com.
