Gina Z. D’Amato, MD, a professor of clinical medicine, assistant director of clinical research, medical director of the Nurse Practitioner Oncology Fellowship Program, and medical director of patient education at the Sylvester Comprehensive Cancer Center and the Miller School of Medicine at the University of Miami.

Dr D'Amato on the Implications of Data With Olaparib Plus Temozolomide in Advanced Uterine Leomyosarcoma  

"[Although] the study didn’t meet its end point, it doesn't mean the combination isn't effective. It's just might not be better than what we have. However, I would still say that it's a potential treatment option."

Gina Z. D’Amato, MD, a professor of clinical medicine, assistant director of clinical research, medical director of the Nurse Practitioner Oncology Fellowship Program, and medical director of patient education at the Sylvester Comprehensive Cancer Center and the Miller School of Medicine at the University of Miami, shared efficacy results and key takeaways from the phase 2/3 Alliance A092104 trial (NCT05432791), which evaluated olaparib (Lynparza) plus temozolomide (Temodar) in advanced uterine leiomyosarcoma.

Although the combination demonstrated promise in early-phase evaluation, the randomized trial ultimately failed to meet its primary progression-free survival (PFS) end point in the biomarker-unselected population, D'Amato stated.

 showed that patients treated with olaparib plus temozolomide (n = 37) had a median PFS of 3.2 months (95% CI, 2.0-7.0) compared with 5.5 months (95% CI, 2.6-10.2) in those who received investigator’s choice of pazopanib (Votrient) or trabectedin (Yondelis; n = 37; stratified HR, 1.16; 95% CI, 0.67-1.99; P = .703). Furthermore, the median overall survival was longer with the investigational regimen at 19.3 months (95% CI, 15.2-not evaluable [NE]) vs 12.9 months (95% CI, 10.4-NE; HR, 0.70; 95% CI, 0.33-1.47), although this finding was not statistically significant. Based on these findings, the trial will be closed for futility on October 1, 2025.

D’Amato noted that the control agents may have overperformed in this population and emphasized that data specific to uterine leiomyosarcoma remain limited for both pazopanib and trabectedin. Furthermore, existing PFS estimates for these agents are extrapolated from broader soft tissue sarcoma populations, complicating statistical assumptions and interpretability, she added.

Despite these negative results, the combination of olaparib/temozolomide may still represent a viable treatment strategy, particularly in real-world practice, and warrants further exploration, D'Amato concluded.

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Gina Z. D’Amato, MD, shares her interpretation of efficacy outcomes from the negative Alliance A092104 trial in advanced uterine leiomyosarcoma.

Dr D'Amato on the Implications of Data With Olaparib Plus Temozolomide in Advanced Uterine Leomyosarcoma

Gina Z. D’Amato, MD, associate professor, assistant director of clinical research, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses optimizing treatment for patients with desmoid tumors.

All patients with desmoid tumors should be observed initially until they develop indications for treatment, D’Amato says. Indications for treatment include tumor growth that could impede or threaten quality of life or cause deformity, dysfunction, or pain. Additionally, growing tumors may be observed, unless they are in areas such as the intra-abdominal wall where other organs can be affected, the head or neck where major blood vessels are involved, or the appendages where they may hinder activity, D’Amato explains.

Historically surgery was the mainstay of treatment for patients with desmoid tumors; however, the field is significantly limiting surgery now because these tumors may regress or disappear without therapeutic intervention, D’Amato says. Now, based on recommendations from the Desmoid Tumor Working Group guidelines, surgery is indicated only in cases where resection will not cause deformity, such as the intra-abdominal wall.

If treatment is indicated, systemic therapy offers patients a less morbid alternative to surgery, D’Amato says. Systemic treatment selection is based on factors, such as tumor location and patient symptoms. Typically, sorafenib (Nexavar) is the recommended first-line therapy and is generally well tolerated. Systemic chemotherapy can also be considered, although it is associated with substantial toxicities, D’Amato concludes.

Funding from SpringWorks Therapeutics/Content Developed Independently by OncLive

Gina Z. D’Amato, MD, discusses optimizing treatment for patients with desmoid tumors.   



Dr. D’Amato on Optimizing Treatment for Patients With Desmoid Tumors  

Gina Z. D'Amato, MD, associate professor and assistant director of Clinical Research, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the importance of multidisciplinary care in sarcoma.

Ensuring that patients with sarcoma are treated with a multidisciplinary approach is a critical component to optimizing their care, says D'Amato. 

A multidisciplinary care team should include medical oncologists, surgeons, radiation oncologists, interventional radiologists, plastic surgeons, and orthopedic oncologists, adds D’Amato. 

With multiple major advances made in the sarcoma space in recent years, the need for multidisciplinary care is becoming more relevant, explains D’Amato. 

In the coming years, novel treatments and developing a greater understanding of sarcoma may continue to move the field forward, concludes D’Amato.

Gina Z. D'Amato, MD, discusses the importance of multidisciplinary care in sarcoma.  



Dr. D’Amato on the Importance of Multidisciplinary Care in Sarcoma 

Gina Z. D'Amato, MD, associate professor and assistant director of Clinical Research, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the limitations of liquid biopsy in sarcoma.

In August 2020, the FDA approved the Guardant360

 CDx liquid biopsy for comprehensive genomic profiling in patients with any solid malignant cancer. 

In the sarcoma space, liquid biopsy is promising, D’Amato says. Prior to the approval, the Guardant360 CDx assay was utilized in sarcoma, mainly for patients with gastrointestinal stromal tumors. 

Additionally, the test was used in patients who had disease progression where tissue was unavailable for testing, explains D’Amato.


Liquid biopsy may have a higher accuracy rate compared with tissue biopsy, D’Amato explains. However, until the technology improves, liquid biopsy will not be used in the adjuvant setting. Currently, patients have to have high tumor burden in order for an alteration to be detected. 

Ongoing research regarding circulating tumor DNA could provide a way to improve the accuracy of liquid biopsy tests among patients with low tumor burden or those without radiographic evidence of disease, concludes D’Amato.

Gina Z. D'Amato, MD, discusses the limitations of liquid biopsy in sarcoma.  



Dr. D’Amato on the Limitations of Liquid Biopsy in Sarcoma 

Gina Z. D'Amato, MD, associate professor and assistant director of Clinical Research, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the diminishing role of chemotherapy in sarcoma.

Although chemotherapy has demonstrated substantial efficacy in many sarcoma subtypes, the treatment is associated with significant toxicity, D’Amato says.

Some sarcoma subtypes are sensitive to particular chemotherapy regimens; however, the majority of chemotherapy is nonspecific as it targets cell division, explains D’Amato.

Understanding drivers of cancer on a molecular level may allow the field to shift from chemotherapy to more specific, less toxic targeted therapies, D’Amato says.

Although it is unlikely that chemotherapy will lose its role in sarcoma in the foreseeable future, precision medicine may have the potential to eliminate the need for chemotherapy in the distant future, concludes D’Amato.

Gina Z. D'Amato, MD, discusses the diminishing role of chemotherapy in sarcoma.  



Dr. D’Amato on the Diminishing Role of Chemotherapy in Sarcoma 

Gina Z. D'Amato, MD, associate professor and assistant director of Clinical Research, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the utility of next-generation sequencing (NGS) in patients with stage I, II, or III sarcoma.

The use of NGS in this patient population largely depends on the sarcoma subtype being treated, D’Amato says. Moreover, some subtypes have different sensitivities to treatments.

In patients with stage I, II, or III sarcomas, standard surgical intervention and radiation therapy, with or without chemotherapy, are used with curative intent, explains D’Amato.

As such, NGS is unnecessary in this setting as there are no data to inform whether patients may benefit from adjuvant targeted therapies, concludes D’Amato.

Gina Z. D'Amato, MD, discusses the utility of next-generation sequencing in patients with stage I, II, or III sarcoma.  



Dr. D'Amato on the Utility of NGS in Stage I, II, and III Sarcoma 

Gina Z. D'Amato, MD, associate professor and assistant director of Clinical Research, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the emerging role of next-generation sequencing (NGS) in sarcoma.

There are different views about NGS, but this approach appears to be very promising, according to D’Amato. Although current information is limited in terms of available targeted treatments, a lot can be learned from the tumor, says D’Amato, and these data can be collected over time to better understand sarcomas. It is best to perform NGS at diagnosis, according to D’Amato.

Reports have said discordance is as high as 15% between different pathologists with the diagnosis of sarcoma because there are more than 170 different subtypes of sarcoma, says D’Amato. If there is a question about the diagnosis, the pathologist can use NGS to help make the diagnosis. About one-third of soft tissue sarcomas will have reciprocal translocations and these can be tested for by using FISH or NGS, concludes D’Amato.

Gina Z. D'Amato, MD, discusses the emerging role of next-generation sequencing in sarcoma.

Gina Z. D'Amato, MD

Articles

Dr D'Amato on the Implications of Data With Olaparib Plus Temozolomide in Advanced Uterine Leomyosarcoma

Dr. D’Amato on Optimizing Treatment for Patients With Desmoid Tumors

Dr. D’Amato on the Importance of Multidisciplinary Care in Sarcoma

Dr. D’Amato on the Limitations of Liquid Biopsy in Sarcoma

Dr. D’Amato on the Diminishing Role of Chemotherapy in Sarcoma

Dr. D'Amato on the Utility of NGS in Stage I, II, and III Sarcoma

Dr. D'Amato on the Emerging Role of Next-Generation Sequencing in Sarcoma