Selinexor Reduces Pain in Patients With Advanced Dedifferentiated Liposarcoma, Study Finds


New data show pain worsened faster, and more dramatically, in patients given placebo versus selinexor for dedifferentiated liposarcoma, as measured by the European Organisation for Research and Treatment of Cancer’s 30-item core quality of life questionnaire.

Patients with advanced dedifferentiated liposarcoma (DDLPS) had less pain and slower worsening of pain when treated with selinexor (Xpovio) compared with placebo, according to new data from the phase 3 portion of the Selinexor in Advanced Liposarcoma (SEAL) trial (NCT02606461).1

The results offer important health-related quality of life (HRQOL) data for the oral selective inhibitor of nuclear export compound, which is currently approved by the FDA to treat relapsed or refractory multiple myeloma and relapsed or refractory diffuse large B-cell lymphoma (DLBCL). It has not yet been approved for DDLPS. The findings were published in the journal Future Oncology.

The primary objective of the study was to compare progression-free survival (PFS) with selinexor versus placebo in 277 patients with advanced unresectable DDLPS. However, a secondary end point of the trial was to examine HRQOL in the 2 arms. To achieve that, the investigators, including corresponding author Mrinal Gounder, MD, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, had the patients to complete the European Organisation for Research and Treatment of Cancer’s 30-item core quality of life questionnaire. Most of the patients in the study (n= 255) completed the survey, which was given at baseline and on day 1 of each treatment cycle through day 169. The patient population had a median age of 65 years and was mostly female (62.1%) and White (77.7%).

The results showed that pain worsened over the course of the study for both the selinexor and placebo arms, but pain scores were worse and increased faster for patients treated with placebo. For instance, at day 127, pain in the placebo group had worsened by an average of 16.16 points, while the selinexor group had worsened by just 3.98 points on average, a gap of –12.18 points (95% CI, –23.31 to –1.06; P = .0320). By day 169, the gap had grown to –14.24 points (95% CI, –27.15 to –1.32; P = .0308), with scores for the selinexor group remaining lower.

“This is consistent with the reported reduction in tumor size in 27.1% of patients treated with selinexor versus 15.5% treated with placebo,” Gounder and colleagues wrote.

Some quality-of-life metrics, including physical function, role function, and global health/quality of life were initially worse in the selinexor group, but by days 127, 85, and 85, respectively, the difference had become statistically insignificant.

The investigators said “the initial worsening may potentially be related to initial side effects of active therapy.”

The study also found patients in the selinexor arm had a longer time to definitive deterioration (TDD) in pain scores. A total of 43.2% of patients in the placebo arm reached definitive deterioration compared with 34.5% of patients in the selinexor group. Patients in the selinexor group also took a median of 8.4 months to reach definitive deterioration compared with 2.9 months in the placebo group.

Gounder and colleagues noted that the study population in the SEAL trial was heavily pre-treated, and there are currently no treatment options available that have been shown to provide a clinical benefit to this population.

Jatin Shah, MD, chief medical officer of Karyopharm, which markets Xpovio, said in a press release that these new data build upon previously reported objective gains in PFS as measured by radiography.2

“Since pain is one of the most devastating symptoms associated with advanced and progressing DDLPS, the significant reduction in pain, and a delay in the time to definitive deterioration reported by patients in the selinexor arm, combined with the convenience of an orally administered therapy, could represent a meaningful clinical benefit to patients,” Shah said.


1. Gounder M, Abdul Razak AR, Gilligan AM, et al. Health-related quality of life and pain with selinexor in patients with advanced dedifferentiated liposarcoma. Future Oncol. Published April 15, 2021. doi:10.2217/fon-2021-0284

2. Karyopharm Announces Publication of Health-Related Quality of Life Outcomes from Phase 3 SEAL Study of Selinexor in Advanced Unresectable Dedifferentiated Liposarcoma in Future Oncology. News release. Karyopharm Therapeutics Inc. April 19, 2021. Accessed May 17, 2021.

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