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Miami Cancer Institute Precision Oncology Symposium

Neeta Somaiah, MD, discusses chemotherapy as the current mainstay of treatment in sarcoma subtypes and the emergence of immunotherapies in the space.

Dr Somaiah on the Role of Chemotherapy in Sarcomas

“We still use chemotherapy to begin with [in treating patients with sarcomas], but there are a lot of targeted therapy options and clinical trials that we think of. For some of the disease subtypes, targeted therapies have replaced chemotherapy, which is quite exciting.”

Neeta Somaiah, MD, professor, department chair, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the role of chemotherapy in the management of sarcomas.

In the realm of sarcomas, chemotherapy is still considered the mainstay of treatment, especially in patients with metastatic or locally advanced disease, Somaiah begins. In the past 5 years, the list of chemotherapy options and regimens has been smaller, she explains. However, she notes that there has been a growing list of immunotherapies and targeted therapies, which continues to expand.

Now, subtypes of sarcomas and more biomarkers are being better established, Somaiah says. Having these identified helps determine optimal treatment options, particularly for rarer subtypes of sarcoma, she adds.

 to afamitresgene autoleucel (afami-cel; Tecelra) for the treatment of patients with unresectable or metastatic synovial sarcoma. Subsequently, in September 2024, the FDA 

approved atezolizumab and hyaluronidase-tqjs

 (Tecentriq Hybreza) for subcutaneous injection for the use of all of the existing adult indications as the intravenous formulation of atezolizumab (Tecentriq), which included alveolar soft part sarcoma, among other solid tumors. Atezolizumab was 

 in December 2022 for the treatment of adult and pediatric patients at least 2 years of age with alveolar soft part sarcoma.

Therefore, the shift from chemotherapy-only regimens to immunotherapies has been seen in select sarcoma subtypes, Somaiah notes. Chemotherapy is typically where treatment starts; nonetheless, more clinical trials and approved immunotherapies are starting to replace the use of chemotherapy, which is exciting, she concludes.

Over the past 5 years, advancements in identifying specific biomarkers within sarcoma subtypes have paved the way for targeted therapies that could potentially replace traditional chemotherapy-based approaches, according to Neeta Somaiah, MD, who adds that such progress in precision medicine is greatly enhancing patient outcomes, particularly for those with rare sarcoma subtypes.

 (afami-cel; Tecelra) in August 2024, which marked the first T-cell therapy for patients with advanced synovial sarcoma, is emblematic of the shift towards more tailored treatment in sarcomas.

 The genetically modified autologous T-cell immunotherapy is indicated for adult patients with unresectable or metastatic synovial sarcoma who were previously treated with chemotherapy; were HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive; and whose tumors express MAGE-A4, identified by FDA-approved or -cleared companion diagnostics.

“We have seen [a growing number of] drug approvals in [sarcoma] in the past 5 years, and this has helped [improve patient outcomes],” Somaiah said. “The extent of benefit [with these regimens] has been much higher, even though we're going after a smaller subgroup of patients.”

®, Somaiah highlighted key points from her presentation on sarcoma at the 

3rd Annual Miami Cancer Institute Precision Oncology Symposium

 the impact of precision oncology on patient outcomes in sarcoma, and novel, more targeted therapies coming down the pike.

Somaiah is a professor and deputy department chair of the Department of Sarcoma Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, Texas. 

: How has the identification of specific biomarkers within sarcoma subtypes influenced drug development and improved patient outcomes?

: Understanding each of the nuances of these different [sarcoma] subtypes helps us find homogenous subtypes with specific biomarkers that can lead to easier and faster identification of drugs. Once we've started dividing our sarcoma subtypes [we will start] having clinical trials specific to these rare subtypes.

Sarcoma is a space where, if you identify the subtype and have a target, investigators shouldn't be worried about investigating a rare tumor. If we come together to perform trials, we can get a drug approval much faster, and we will see the benefits [much quicker. Some patients are very young, and being able to [offer them] targeted therapy options that provide fewer adverse effects and better quality of life can make a dramatic difference [in outcomes].

Sarcomas have historically been treated with chemotherapy, radiation therapy, and surgery. How are precision medicine approaches reshaping the traditional treatment paradigm?

We have a small number of chemotherapy options that we treat sarcoma patients with, and that list has not expanded significantly in the past 5 years. It's the same drugs with a few shifts. The majority of [patients with] sarcomas are still [receiving] chemotherapy as their mainstay [treatment] for advanced or locally advanced disease. However, when you look at the growing list of targeted therapies and immunotherapy agents, that list is quite large and is still expanding.

It's encouraging to know that as we're identifying these subtypes [of sarcoma], are finding biomarkers, and a able to match [them with] targeted drugs, we have seen an improvement in outcomes for some of these rare subtypes. We still use chemotherapy to begin with, but there are a lot of targeted therapy options and clinical trials that we consider. For some of the disease subtypes, these targeted therapies have replaced chemotherapy, which is quite exciting.

What are some of the key challenges in developing novel therapies for sarcoma? How can early evaluations and multidisciplinary care address some of these difficulties?

For sarcoma, I think the biggest challenge that remains is the rarity of the disease. With this also comes the path diagnosis of the subtypes [of sarcoma]. The big push is still to make sure that [patients with] sarcomas get at least an early opinion at an expert center that also involves a pathologic review. We still need to consider that some people will send off the next-generation sequencing up front, which is happening quite a bit but is absolutely essential. We also need to match it with the pathologic diagnosis because there are nuances within sarcoma based on where the tumors arise, where they're going to metastasize, which ones need early systemic therapy, and where you can delay those therapies. Having a multidisciplinary approach [is necessary] to treat [patients with] these sarcomas. The challenge is getting [patients] to an expert center that understands these nuances and [provides] an accurate diagnosis.

We can make great progress if we can institute the right treatment early, which is why an early opinion does help guide the care of these patients. In terms of the rarity [of sarcomas], the other challenge is that when we do large trials, they are registrational—we're trying to get drugs approved. We have to work with expert sarcoma centers within the United States as well as globally. The good thing is that we can perform these trials quickly when there is a good drug and the subtypes are there, even if the incidence of the tumor is [rarer].

What ongoing research with novel agents and tailored treatment approaches could advance the sarcoma treatment paradigm?

In the sarcoma world, there are some targeted therapies, like you'll see for desmoid sarcoma. There's a new gamma secretase inhibitor that's being looked at. There's more work done with specific mutations that are not sarcoma-specific but across different subtypes. Last year, the first T-cell therapy [afamitresgene autoleucel] was FDA approved for [advanced synovial] sarcoma. That field is still nascent, and we're going to see a lot of work in that field moving forward because there are more cellular therapies that are going to emerge. The goal would be to expand [these agents] to more sarcoma subtypes with the same markers, as well as to patients with HLA subtypes that are beyond what the current T-cell therapies are approved for.

[It’s important to understand the optimal application of] immunotherapy in terms of which patients benefit and what the right combinations are. Are there some CTLA-4 [therapies] that are better than other others, that will [show] a response in sarcomas that are traditionally cold? How do we identify those patients and [disease] subtypes better, and actually get some of these newer agents that we're seeing in clinical trials targeting sarcomas? That field is going to expand, and we're going to see a lot there.

The field of antibody-drug conjugates [ADCs], though not specific to sarcomas, is also quite exciting. As we see these phase 1 trials come along, we'd be interested in seeing [research with] sarcomas that have applicable targets for these ADCs. I am seeing a lot of trials in that space, so I'm excited to see what that brings this year.

We're talking about sarcomas, but [gastrointestinal stromal tumors (GIST)] are another big category [of interest]. That field is going to see some practice-changing drugs [emerge], and perhaps a change in the way we sequence drugs for the treatment of GIST, is yet to come.

Somaiah N. Dividing and conquering sarcomas. Presented at: Third Annual Miami Cancer Institute Precision Oncology Symposium; February 7-8, 2025; Coral Gables, FL.

FDA approves first gene therapy to treat adults with metastatic synovial sarcoma. FDA. August 2, 2024. Accessed February 11, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-afamitresgene-autoleucel-unresectable-or-metastatic-synovial-sarcoma

Advancements in biomarker identification within sarcoma subtypes have led to the development of targeted therapies, improving patient outcomes and potentially replacing traditional chemotherapy. The FDA's approval of afamitresgene autoleucel marks a significant shift towards personalized treatment for synovial sarcoma. Despite challenges due to the rarity of sarcomas, early expert evaluation and multidisciplinary care are crucial. Ongoing research in targeted therapies, immunotherapy, and antibody-drug conjugates is expected to further transform the sarcoma treatment landscape, with promising developments in gastrointestinal stromal tumors as well.

Neeta Somaiah, MD, highlights the evolving sarcoma treatment paradigm within the past 5 years, including the FDA approval of afamitresgene autoleucel. 

Biomarker-Driven Research Accelerates Drug Discovery and Precision Medicine Approaches in Sarcoma 

Dr Ahluwalia on the Evolution of Precision Medicine in Oncology

“I could not be more thrilled about the remarkable pace of transformative changes that we are collectively making in oncology. We are living in the best era of mankind, where we have artificial intelligence, which can help us with finding better information with the genomic testing that we offer to all of our patients who come to see us at Miami Cancer Institute.”

Manmeet Singh Ahluwalia, MD, MBA, FASCO, chief scientific officer, chief, medical oncology, deputy director, Fernandez Family Endowed Chair in Cancer Research, Baptist Health Miami Cancer Institute, discusses advances in oncology research and patient care across cancer types that were highlighted at the Third Annual Miami Cancer Institute Precision Oncology Symposium.

The field of oncology is undergoing a rapid and transformative evolution, driven by advancements in artificial intelligence, genomic testing, and precision medicine, Ahluwalia begins. At Miami Cancer Institute, a multidisciplinary cancer management approach ensures patients receive individualized treatment strategies based on the latest scientific insights, he says. Meetings such as the Miami Cancer Institute Precision Oncology Symposium serve as crucial platforms for disseminating groundbreaking information, allowing for the continuous refinement of treatment protocols, he explains.

Significant progress has been made across multiple oncology specialties, with stage IV lung cancer serving as a prime example, according to Ahluwalia. Approximately 2 decades ago, the median overall survival (OS) for these patients was approximately 12 months, and the 5-year OS rate was approximately 5%, he notes. Now, however, the median OS in this population has extended to approximately 2.5 years, with 5-year survival rates reaching approximately 20%, he reports.

Miami Cancer Institute places a strong emphasis on remaining at the forefront of scientific and clinical advancements, Ahluwalia states. Strategic partnerships with institutions like Florida International University facilitate translational research, bridging the gap between bench discoveries and bedside applications, he says. Additionally, collaborations with leading cancer centers worldwide foster valuable exchanges of expertise and novel therapeutic strategies, he concludes.

Manmeet Singh Ahluwalia, MD, MBA, FASCO, discusses oncology advances that were highlighted at the Miami Cancer Institute Precision Oncology Symposium.

Dr McCann on the Treatment Paradigm for HER2+ Breast Cancer With Brain Metastases

“The big challenge in treating patients with HER2-positive breast cancer is that they can develop brain metastases later on, and this is challenging because we don’t have a lot of therapies that cross the blood-brain barrier.”

Kelly E. McCann, MD, PhD, assistant professor, breast medical oncologist, UCLA, discusses current and evolving treatment strategies for patients with HER2-positive breast cancer who develop brain metastases.

A major challenge in the management of HER2-positive breast cancer is the development of brain metastases, which are a therapeutic hurdle due to the limited ability of many systemic agents to cross the blood-brain barrier, McCann begins. HER2-targeted TKIs—including pan-HER inhibitors like neratinib (Nerlynx)—have demonstrated intracranial activity, she says.

Additionally, the phase 2 HER2CLIMB trial (NCT02614794), which evaluated the efficacy of tucatinib (Tukysa) in combination with trastuzumab (Herceptin) and capecitabine in previously treated patients with HER2-positive metastatic breast cancer, uniquely included a significant proportion of patients with brain metastases, a population often excluded from clinical trials, she explains. An exploratory subgroup analysis of this trial showed that at a median follow-up of 29.6 months (range, 0.1-52.9), among the 291 patients with brain metastases (47.5% of the total study population), the tucatinib-based regimen led to a median overall survival of 21.6 months (95% CI, 18.1-28.5) vs 12.5 months (95% CI, 11.2-16.9) with placebo plus trastuzumab and capecitabine. Moreover, the duration of intracranial response was 8.6 months (95% CI, 5.5-10.3) in the tucatinib arm vs 3.0 months (95% CI, 3.0-10.3) in the placebo arm.

Furthermore, emerging data indicate that fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) may also penetrate the blood-brain barrier, according to McCann. Its proposed mechanism of action involves the intracellular release of its cytotoxic payload, which may then diffuse across the blood-brain barrier, as opposed to the full antibody-drug conjugate itself crossing intact, she notes. Therefore, T-DXd is a potential therapeutic strategy for patients with HER2-positive breast cancer with brain metastases, and warrants further investigation in this population, she concludes.

Kelly E. McCann, MD, PhD, discusses current and evolving treatment strategies for patients with HER2-positive breast cancer who develop brain metastases.

Neeta Somaiah, MD, discusses ongoing research with novel agents that have emerged and those that could soon emerge in the sarcoma treatment paradigm.

Dr Somaiah on Ongoing Research With Novel Agents in Sarcomas

“[In 2024,] the first T-cell therapy was approved [for advanced synovial sarcoma]. I think that field is still nascent, and we’re going to see a lot of work in that field moving forward because there are more cellular therapies that are going to come forward in that area.”

Neeta Somaiah, MD, professor, department chair, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses ongoing research with novel agents that may potentially alter the sarcoma treatment paradigm.

Although chemotherapy remains highly prevalent in the sarcoma treatment paradigm, more targeted therapies have emerged and are being developed, specifically for desmoid sarcomas, Somaiah begins, highlighting ongoing work with gamma-secretase inhibitors. A phase 3 trial (NCT03785964) evaluated the gamma-secretase inhibitor nirogacestat for the treatment of desmoid sarcoma, in which patients were randomly assigned to be treated with either nirogacestat (n = 70) or placebo (n = 72). Data demonstrated that patients treated with nirogacestat experienced a significant progression-free survival benefit compared with placebo (HR, 0.29; 95% CI, 0.15-0.55; 

 < .001). Of note, the likelihood of being event-free at 2 years was 76% vs 44% in the nirogacestat and placebo arms, respectively.

FDA granted accelerated approval to afamitresgene autoleucel

 (afami-cel; Tecelra) for the treatment of patients with unresectable or metastatic synovial sarcoma, which was the first T-cell therapy approved for sarcoma, Somaiah says. The FDA’s decision was supported by data from cohort 1 of the phase 2 SPEARHEAD-1 trial (NCT04044768). Among patients treated with afami-cel (n = 44), the overall response rate was 43% per independent review assessment; the complete response rate was 4.5%. The median duration of response (DOR) was 6 months (95% CI, 4.6–not reached), and the 12-month DOR rate was 39%. Somaiah concludes that although the treatment landscape for sarcomas is still developing, new therapies are on the horizon, notably for patients within specific sarcoma subtypes.