Dimitrios Nasioudis, MD, discusses preclinical study findings utilizing XPO1 inhibition for TP53 wild-type low-grade serous and clear cell ovarian cancer.

Dr Nasioudis on the Potential for XPO1 Inhibition in TP53 Wild-Type Ovarian Cancer

“We did see significant antitumor activity of XPO1 [inhibition with] selinexor, both in vitro as well as in vivo, and we did not see as good activity in 

-mutant tumors. We do feel that these results indicate that this genomic characteristic—[

 wild-type]—can be capitalized on in the clinic with XPO1 inhibition.”

Dimitrios Nasioudis, MD, assistant professor, obstetrics and gynecology, Perelman Center for Advanced Medicine, the University of Pennsylvania, discusses findings from a preclinical study regarding the use of XPO1 inhibition in low-grade serous (LGSOC) and clear cell ovarian cancer (CCOC).

Approximately 95% of patients with LGSOC and 85% of patients with CCOC do not harbor 

 is a gene that encodes P53, a key protein that acts as a tumor suppressor, he continues. However, he notes that this genomic finding has not translated into a therapeutic strategy. Thus, Nasioudis and colleagues hypothesized that utilizing XPO1 inhibition with selinexor (Xpovio) could lead to effective antitumor activity. XPO1 exports 

 genes from the nucleus to the cytoplasm, he says, which is why inhibiting it may be an effective target.

2024 SGO Annual Meeting on Women’s Cancer

, showed significant antitumor activity in vitro and in vivo with the use of selinexor. However, antitumor activity was lower in 

-mutant tumors, he says. The result of their findings demonstrated that XPO1 inhibition could serve as a potential therapeutic strategy for patients with TP53 wild-type LGSOC or CCOC, according to Nasioudis.

He states that the next steps of research will include exploring the mechanism of resistance to XPO1 inhibition in vitro and in vivo. Following this step, he and his colleagues will try to capitalize the results from the study through an early phase clinical trial with patients with LGSOC and CCOC, Nasioudis concludes.

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Dimitrios Nasioudis, MD, discusses preclinical study findings utilizing XPO1 inhibition for TP53 wild-type low-grade serous and clear cell ovarian cancer. 

Dr Nasioudis on the Use of SLNB in Metastatic Vulvar Squamous Cell Carcinoma

Dimitrios Nasioudis, MD, fellow, Gynecologic Oncology, Perelman School of Medicine, the University of Pennsylvania, discusses findings from a study investigating outcomes of real-world patients with early-stage, metastatic vulvar squamous cell carcinoma who underwent sentinel lymph node biopsy (SLNB).

For patients with negative nodes per SLNB, the long-term outlook was promising, with a 5.2% to 7% incidence of groinal recurrence, even in the absence of additional treatment, Nasioudis begins. Conversely, patients with micrometastases faced a considerably heightened risk of groinal and/or distant disease recurrence, particularly if they opted out of receiving adjuvant treatment, with approximately 40% of these patients experiencing such recurrence, he states. This finding underscores the importance of intervention in this cohort to mitigate the risk of disease progression, Nasioudis adds.

Moreover, there exists a discernible variability in the approaches to treating patients with micrometastases, he expands. Some health care providers opt for external beam radiation therapy alone, others advocate for a combination of external beam radiation therapy and inguinal femoral lymphadenectomy, and others recommend inguinal femoral lymphadenectomy as a standalone procedure, Nasioudis explains. This disparity underscores the inconsistency and lack of standardized guidelines in the treatment practices for this patient population, he says.

The ongoing phase 3 GROINSS-VIII study is investigating whether inguinal femoral lymphadenectomy can be safely omitted in the treatment of these patients and whether chemoradiation presents a viable treatment alternative, Nasioudis continues. The results of this study will provide valuable insights into optimizing treatment strategies for patients with micrometastases, potentially streamlining care and improving outcomes, he elucidates, adding that patients who undergo radiosensitized chemotherapy exhibit a trend toward lower recurrence rates. This observation raises intriguing possibilities for improving treatment efficacy in this population, according to Nasioudis.

Given these findings, Nasioudis says investigators are eager to delve deeper into the dataset to conduct a more comprehensive analysis and confirm the potential benefits of radiosensitized chemotherapy. This further exploration may yield valuable insights into refining treatment protocols and ultimately enhancing patient outcomes in this challenging clinical scenario, he concludes.

Disclosures: Dr Nasioudis reports no financial relationships.

Dimitrios Nasioudis, MD, discusses outcomes of patients with metastatic vulvar squamous cell carcinoma who underwent sentinel lymph node biopsy.

Dimitrios Nasioudis, MD, physician, fellow, gynecologic oncology, Department of Obsetrics and Gynecology, University of Pennsylvania, Penn Medicine, discusses how the use of next-generation sequencing (NGS) can help identify the unique molecular profile of endometroid ovarian cancer.

As endometroid ovarian cancer is a rare histologic subtype of ovarian cancer, identifying its distinct molecular profile is important for improving treatment in this patient population. To accomplish this, a multicenter study was designed to determine the prevalence of specific genomic alterations associated with this molecular subtype, Nasioudis begins. Researchers analyzed prospective data from the AACR Project GENIE v13.0 genomic database to identify patients with endometroid ovarian cancer, Nasioudis explains. The database contains de-identified molecular NGS data from patients being treated at 18 different institutions. The trial also utilized data from the OncoKB database to evaluate the presence of pathogenic gene alterations.

 alterations at 39% and 38% respectively, Nasioudis continues. Other prevalent mutations included 

 had the lowest prevalence at 21%. Notably, the exclusivity of 

mutations compared with the other alterations indicates that endometroid ovarian cancer is a distinct subtype with its own specific molecular profile, Nasioudis notes. Additionally, the prevalence of these 

 mutations indicates a future avenue of investigation.

Ultimately, this trial also demonstrates the utility of NGS in identifying actionable mutations for continued research on the development of targeted therapeutics, and guides enrollment in basket trials, Nasioudis states. Moreover, data obtained from NGS can inform treatment decisions, Nasioudis concludes.

Dimitrios Nasioudis, MD, discusses how the use of next-generation sequencing can help identify the unique molecular profile of endometroid ovarian cancer. 


Dimitrios Nasioudis, MD

Articles

Dr Nasioudis on the Potential for XPO1 Inhibition in TP53 Wild-Type Ovarian Cancer

Dr Nasioudis on the Use of SLNB in Metastatic Vulvar Squamous Cell Carcinoma

Dr Nasioudis on the Use of NGS to Identify the Molecular Profile of Endometroid Ovarian Cancer