Surgical Treatment for Gynecologic Cancer

Panelists discuss how LEAP-001, despite missing primary endpoints, suggested meaningful activity for lenvatinib plus pembrolizumab in dMMR and post-adjuvant subgroups who may need alternatives to standard frontline chemotherapy. 

Endometrial Cancer- Interpreting dMMR and Post-Adjuvant Activity from LEAP-001

LEAP 001 was designed to evaluate whether a chemo free regimen of lenvatinib plus pembrolizumab could outperform standard carboplatin and paclitaxel in the frontline setting. Although the study did not meet its co primary endpoints, meaningful activity signals emerged within key subgroups. Patients with dMMR tumors showed stronger responses to the combination, consistent with the well established sensitivity of this molecular group to immunotherapy. Patients who had previously received adjuvant carboplatin and paclitaxel, often a more difficult population to treat, also demonstrated encouraging benefit. These trends do not alter the overall trial interpretation but highlight subgroups that may benefit more than others. As experts noted, the findings support individualized consideration of the regimen, particularly for patients who are not suitable candidates for standard frontline chemotherapy.

Videos

Endometrial Cancer: Interpreting dMMR and Post-Adjuvant Activity from LEAP-001 

Panelists discuss how advanced/recurrent endometrial cancer has remained a high unmet need due to years of minimal survival gains with carboplatin/paclitaxel until immunotherapy began shifting outcomes. 

Endometrial Cancer Today- Defining the Persistent Unmet Needs in Advanced and Recurrent Disease

Advanced and recurrent endometrial cancer has long represented a major unmet clinical need because systemic treatment options remained unchanged for more than a decade. Carboplatin plus paclitaxel became the long standing standard after GOG209 showed non inferiority to TAP, but this did not translate into meaningful survival improvement. Progression free survival remained limited and over half of patients eventually died from their disease. Without new therapies, clinicians had few effective tools to alter the natural history of advanced or recurrent presentations, resulting in modest and short lived responses. These limitations persisted until the introduction of immune checkpoint inhibitors around 2018, which marked the first major therapeutic advance in many years. The long period of stagnation underscores why unmet needs remain significant and highlights the importance of continued innovation to improve long term outcomes.

Panelists discuss how advanced/recurrent endometrial cancer has remained a high unmet need due to years of minimal survival gains with carboplatin/paclitaxel until immunotherapy began shifting outcomes.

Endometrial Cancer Today: Defining the Persistent Unmet Needs in Advanced and Recurrent Disease 

Dr Miller on the Efficacy of Selinexor in TP53 Wild-Type Endometrial Cancer  

David S. Miller, MD, professor, Department of Obstetrics and Gynecology, Dallas Foundation Chair in Gynecologic Oncology, Amy and Vernon E. Faulconer Distinguished Chair in Medical Science, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, discusses the efficacy of treatment with selinexor (Xpovio) in patients with advanced or recurrent 

 wild-type endometrial cancer based on updated data from the exploratory subgroup analyses of the phase 3 SIENDO study (NCT03555422).

These prespecified subgroups analyses evaluated the long-term efficacy and safety of selinexor maintenance, Miller begins. Findings were initially presented at the 2024 

, with longer-term follow-up data subsequently reported at the International Gynecologic Cancer Society 2024 Annual Global Meeting.

In this recent analysis which evaluated patients according to mismatch repair status, selinexor significantly extended progression-free survival (PFS) compared with placebo in patients with 

 wild-type, mismatch repair–proficient (pMMR) disease, Miller reports. After a median follow-up of 38.5 months, patients receiving selinexor (n = 47) achieved a median PFS of 39.5 months (95% CI, 19.3-not reached [NR]) vs 4.9 months (95% CI, 2.0-NR) with placebo (n = 23; HR, 0.36; 95% CI, 0.19-0.71; one-sided nominal 

= .0011). However, this improvement was less pronounced in patients with mismatch repair–deficient (dMMR) disease, who typically respond well to immune therapy, he notes. Among patients with dMMR, 

 wild-type disease (n = 29), selinexor (n = 20) produced a median PFS of 13.1 months (95% CI, 3.6-NR) vs 3.7 months (95% CI, 1.9-NR) with placebo (n = 9) following 32.8 months of median follow-up (HR, 0.49; 95% CI, 0.18-1.34; one-sided nominal 

Although overall survival (OS) data in the 

 wild-type subgroup remain immature, preliminary results show a trend in favor of selinexor (HR, 0.65); median OS has not yet been reached, Miller adds. 

Additionally, an analysis of quality-adjusted time without symptoms or toxicity demonstrated a meaningful increase in quality- and toxicity-adjusted PFS with selinexor, showing a difference of 10.63 months compared with placebo. For the 

 wild-type, pMMR group, selinexor conferred a PFS benefit of 12.70 months relative to placebo. These data suggest that selinexor may be particularly beneficial for patients with 

 wild-type, pMMR disease, providing extended disease control and improved quality of life, Miller concludes.

David S. Miller, MD, discusses the efficacy of selinexor in patients with advanced or recurrent TP53 wild-type endometrial cancer. 

Dr Miller on the Efficacy of Selinexor in TP53 Wild-Type Endometrial Cancer

Long-term Follow-up of Selinexor Maintenance for Patients With TP53wt Advanced or Recurrent Endometrial Cancer: A Prespecified Subgroup Analysis From the Phase 3 ENGOT-EN5/GOG-3055/SIENDO Study

David Miller, MD, reviews a plenary presentation (originally presented at the ASCO 2024 Annual Meeting by Vikky Makker, MD) on the long-term follow-up of the ENGOT-EN5/GOG-3055/SIENDO trial, focusing on selinexor maintenance for patients with TP53 wild-type advanced or recurrent endometrial cancer.

, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, 

 covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s episode, sponsored by Karyopharm Therapeutics, we had the pleasure of speaking with David Miller, MD, about the long-term follow-up of the subgroup analysis of the phase 3 SIENDO trial (NCT03555422) investigating selinexor maintenance therapy in patients with 

 wild-type advanced or recurrent endometrial cancer. Dr Miller is a professor and chief of the Division of Gynecologic Oncology in the Department of Obstetrics and Gynecology, as well as the Amy and Vernon R. Faulconer Distinguished Chair in Gynecologic Oncology at the University of Texas (UT) Southwestern Medical School in Dallas. He is also the medical director of the UT Southwestern Harold C. Simmons Cancer Center.

In our exclusive interview, Dr Miller discussed unmet needs in the endometrial cancer treatment paradigm that led to the initiation of SIENDO, key updated efficacy findings from the subgroup analysis in patients with 

 wild-type disease, and what the future for selinexor development may look like in this patient population.

That’s all we have for today! Thank you for listening to this episode of 

, sponsored by Karyopharm Therapeutics. Check back on Mondays and Thursdays for exclusive interviews with leading experts in the oncology field.

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Podcasts

Dr Miller discusses findings from the SIENDO trial of selinexor maintenance therapy in patients with TP53 wild-type advanced endometrial cancer.

David Miller, MD

Articles

Endometrial Cancer: Interpreting dMMR and Post-Adjuvant Activity from LEAP-001

Endometrial Cancer Today: Defining the Persistent Unmet Needs in Advanced and Recurrent Disease

Dr Miller on the Efficacy of Selinexor in TP53 Wild-Type Endometrial Cancer

Long-term Follow-up of Selinexor Maintenance for Patients With TP53wt Advanced or Recurrent Endometrial Cancer: A Prespecified Subgroup Analysis From the Phase 3 ENGOT-EN5/GOG-3055/SIENDO Study

Miller Discusses the Use of Selinexor in TP53 Wild-Type Advanced Endometrial Cancer