The pace of progress in cancer research keeps getting faster and faster. However, the results of this research can take time to reach the medical community. The ASCO Plenary Series is a program developed by the American Society of Clinical Oncology (ASCO) to help speed the delivery of high-impact cancer research. In this series, cancer care providers gather online to learn about new, carefully selected research and discuss the study results with their colleagues.
The July 2023 session in the ASCO Plenary Series features this study:
- Maintenance therapy with selinexor delays cancer growth in people with advanced or recurrent TP53 wild-type endometrial cancer
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Maintenance therapy with selinexor delays cancer growth in people with advanced or recurrent TP53 wild-type endometrial cancer
Who does this study affect: People with advanced or recurrent TP53 wild-type endometrial cancer who have received previous treatment. Endometrial cancer is also called uterine cancer.
What did this study find: The phase 3 SIENDO clinical trial found that maintenance therapy with the targeted therapy drug selinexor (Xpovio) helped delay cancer growth in people with advanced or recurrent TP53 wild-type endometrial cancer. When a cancer treatment stops or shrinks the disease, maintenance therapy is given after the initial treatment to help reduce the risk of the cancer coming back or delay cancer growth.
About half of all people with advanced or recurrent endometrial cancer have TP53 wild-type tumors. “Wild-type” means that the TP53 gene is found in its natural, unmutated form. People with this diagnosis typically receive initial treatment with chemotherapy, sometimes in combination with radiation therapy or surgery. As there are currently no maintenance therapies approved for people with this diagnosis, patients are usually carefully observed after initial treatment until their cancer comes back, at which point they receive the next line of treatment. For many patients, the cancer will return shortly after initial treatment.
Selinexor is a type of targeted therapy called a “selective inhibitor of nuclear export (SINE).” SINEs block the exportin 1 (XPO1) protein, which is responsible for removing proteins from the nucleus of the cell. This can include removing a type of protein called a “tumor suppressor protein” that helps stop cancer cells from growing. By blocking XPO1, selinexor helps tumor suppressor proteins perform their function of slowing or stopping cancer cell growth. One type of tumor suppressor protein is p53, which is made by the TP53 gene. In this study, researchers wanted to learn whether maintenance therapy with selinexor could help delay cancer growth in people with TP53 wild-type tumors.
The SIENDO study included 113 people with advanced or recurrent TP53 wild-type endometrial cancer that had shrunk following initial treatment. The study participants were randomly assigned to receive maintenance therapy with either selinexor (77 participants) or placebo (36 participants).
At a median follow-up of 25.3 months, the study found that maintenance therapy with selinexor significantly increased the length of time until the cancer grew. The median is the midpoint, meaning half of the participants were followed for less than 25.3 months and half were followed for longer. Overall, selinexor delayed cancer growth for a median of 27.4 months versus 5.2 months with placebo. These results supported findings from an earlier analysis of the study, which showed a delay in cancer growth and a decreased risk for death in those with TP53 wild-type tumors who received selinexor.
The most common serious side effects in the selinexor group that did not occur in the placebo group were low white blood cell count, called neutropenia (18% of participants); nausea (12%); and low platelet count, called thrombocytopenia (9%). About 15% of participants in the selinexor group stopped treatment due to side effects.
What does this mean for patients: Selinexor may help delay cancer growth in people with advanced or recurrent TP53 wild-type endometrial cancer, potentially providing these patients with an effective maintenance therapy option.
“This is an exciting step forward in potential treatment options that will be studied further. With a weekly oral dose of selinexor, there is a possibility to remain progression-free for a much longer period than the current standard of care and substantially delay the initiation of second-line therapy.”
— lead study author Brian M. Slomovitz, MD
Mount Sinai Medical Center
Miami Beach, Florida