On October 23, 2015, trabectedin (Yondelis) was approved by the FDA after promising results from the phase III ET743-SAR-3007 trial. Trabectedin is used to treat patients with advanced soft tissue sarcoma, including liposarcoma and leiomyosarcoma subtypes, and specifically those who have previously received chemotherapy that included an anthracycline.

In the open-label, multicenter, phase III SAR-3007 trial, trabectedin reduced the risk of disease progression by 45% versus dacarbazine in patients with advanced soft tissue sarcoma. There was also a slight survival trend with trabectedin, but the results were not significant.

The trial compared trabectedin with dacarbazine in 518 patients with liposarcoma and leiomyosarcoma who previously received an anthracycline-containing regimen followed by at least one additional line of chemotherapy. The protocol required patients to have an ECOG performance status of 0 or 1. The study was conducted at 85 sites in four different countries, but 94% of the patients were enrolled in the United States.

, Shreyaskumar R. Patel, MD, professor, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, and Jonathan C. Trent, MD, professor of Medicine, co-director, Musculoskeletal Center, Sarcoma Medical Research Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, discussed the use of trabectedin and the future of the treatment paradigms in soft tissue sarcoma.

What have been some of the challenges toward evidence-based treatment in soft tissue sarcoma and how is that evolving?

One of the biggest challenges is that this is a rare group of tumors. Of the 1,650,000 or so new cancers diagnosed in the calendar year 2015, soft tissue sarcomas are just under 12,000 cases. As a group of diseases, it's rare. The added complexity is that the soft tissue sarcomas umbrella is comprised of 50 to 75 subtypes of sarcomas.

The three or four of the more common ones tend to be liposarcomas, leiomyosarcomas, and differentiated biomorphic sarcomas, but the list of entities that fall within this group of tumors that we call soft tissue sarcomas is very long. Consequently, what ends up happening is, to try to get level one evidence, you would need a large sample size in a very homogenous population. That's virtually impossible. Compare this to breast cancer, for example, where there are clearly more than 200,000 new cases in a given calendar year. The heterogeneity is a lot less than it is for soft tissue sarcomas. Consequently, it's not impractical.

As a matter of fact, it is standard practice to run between 2000 and 4000 patient clinical trials in the breast cancer population, in a uniform or homogenous population, to obtain the right answers that would constitute that level one evidence. That's virtually impossible in soft tissue sarcomas. You may run into several trials that may show a 10% difference in the primary endpoint in favor of an experimental arm versus the control arm, but the

-value may not be significant because the sample size is small. This is one of the major issues that we run into.

From a statistical standpoint, you really do want larger clinical trials and to get a large number of patients in a reasonable period of time. Of course, "reasonable" as defined by the sponsors and investigators, collectively. You then end up lumping a lot of patients together, and as I typically said, "you make a fruit salad out of the patient population." You mix apples, pears, peaches, and oranges, which makes the data that much less interpretable, if you will. To try to just test the apples, it will take a very, very long time, and that's the major limitation with soft tissue sarcomas.

Is there anything being done about it? I think over the last several years, the international community has come together. There are examples of trials that are run on both sides of the Atlantic, or even extending over to Asia, Australia, and beyond, to try to get behind a given trial that may be of interest to see if we can try to homogenize, if you will, the population as best as we can.

The management of sarcoma patients has always been challenging in terms of an evidence-based approach. There are a number of studies, but these clinical trials and other studies tend to be small. They tend to be limited in the focus on specific types of sarcomas. This is not surprising when there"s only 10,000 to 15,000 new patients per year diagnosed with sarcoma in the United States, and there are over 50 different types of sarcoma. It can be really challenging to have robust data and large numbers of patients.

That being said, there have been a number of randomized studies recently that have asked several specific questions. For instance, there was a recent study asking whether the use of gemcitabine/docetaxel was better than using an anthracycline such as doxorubicin in frontline therapy for patients with metastatic sarcoma. The result of that study was that doxorubicin was better tolerated and probably more effective than the combination of gemcitabine/docetaxel. Another study recently led to the approval of pazopanib in the treatment of patients with soft-tissue sarcoma, including liposarcoma and GI stromal tumors. This was based on a phase III study comparing pazopanib to placebo in patients with metastatic sarcoma.

A more recent study looked at the use of trabectedin in patients with liposarcoma or leiomyosarcoma. This subset of patients had metastatic disease, and the patients were randomized to either trabectedin or dacarbazine. The result of the study was superiority of the trabectedin arm.

You can see that there are a number of studies that are enrolling a larger number of patients, some of these in specific histologies such as the trabectedin study, which looked at liposarcomas and leiomyosarcoma.

What is the most effective method for a diagnosis and grading soft tissue sarcoma, and how important is molecular genetic testing?

The histopathologic diagnosis part of the disease is fairly well standardized. If patients are presenting with a lump or a mass, we will get a biopsy. The tissue is, and should be, analyzed by pathologists with expertise in musculoskeletal pathology. The characteristics of each one of these 50 to 100 different subtypes, depending on how many you're lumping under the umbrella of sarcomas, is reasonably well defined. Pathologists with expertise will not have difficulty in making the diagnosis.

I think the molecular genetics portion of this particular group of sarcomas is a different story. We will slowly, but steadily, be peeling away at some of the smaller subsets. Where there are characteristic translocations, for example, there may be fusion probings that can be identified to try to help from a diagnostic standpoint, assign a specific name to that particular entity.

Sarcomas have always been a challenging type of cancer to diagnose and grade. There are 10,000 to 15,000 new sarcoma patients per year in the United States compared with somewhere near 200,000 women diagnosed with breast cancer. This is a very rare disease. To make it more complicated, there are over 50 different types of sarcoma. In any individual type, there may only be several hundred or several thousand cases diagnosed per year in the United States. The rarity of this tumor makes it challenging for pathologists to make the diagnosis and assess the grade of the tumor.

At the University of Miami Sylvester Comprehensive Cancer Center, we have our sarcoma pathologists review all new cases in all new patients that come to our site. I think that the critical first step in understanding how to treat a patient with a sarcoma is making the right diagnosis. I generally recommend have the material reviewed at a sarcoma center by a sarcoma specialty pathologist.

In what population of patients would first-line chemotherapy be most appropriate?

I don't think these decisions are any different for soft tissue sarcomas than most other malignancies. Soft tissue sarcomas is more common in the fifth and sixth decade of life, so most of these patients tend to have a reasonable or a very decent performance status, even when they present with metastatic disease, organ function and performance status is acceptable enough for consideration of front-line systemic therapy. This is unlike some of the other epithelial tumors that may be far more widespread, where patients, either because of organ dysfunction, poor performance status, or just personal choice, would not be candidates for any line of systemic therapy. That proportion happens to be relatively small for the group of patients with soft tissue sarcomas.

In my practice, and in my experience, I think most of these patients with metastatic soft tissue sarcomas will end up going through multiple different lines of chemotherapy, or targeted therapies, or experimental trials, simply because they do tend to maintain and preserve their performance status and organ function for quite a long time.

Frontline chemotherapy is used in a variety of different situations in patients diagnosed with sarcoma. A patient is diagnosed with a primary tumor if the metastatic potential is high such as rhabdomyosarcoma, Ewing"s Sarcoma, desmoplastic small-round-cell tumor, osteosarcoma, these are patients that we initiate on chemotherapy as their frontline surgery, generally even before surgery or radiation therapy. In the metastatic setting, chemotherapy is the mainstay of treatment. These patients may get surgery or radiation at some point in the future, but in the setting of metastatic disease, the primary goal is to use systemic therapy to really control, shrink, hopefully even induce a complete remission for patients with metastatic sarcoma.

Who would be the right patient to receive trabectedin?

Trabectedin recently got approved for patients with metastatic or advanced leiomyosarcomas and liposarcomas. This was based on the way the clinical trial was designed. If you follow the prescribing information, then this would be appropriate for patients with leiomyosarcomas and liposarcomas who have metastatic disease, have advanced incurable disease, and who have failed at least one prior line of therapy that included anthracycline. This is the eligibility criteria for the clinical trial that led to the approval of this drug.

Certain subsets like a patient with myxoid liposarcoma are supposed to have exquisite sensitivity to this drug trabectedin, and if there were issues or contraindications to conventional anthracycline-based therapy, this [trabectedin] certainly can be moved up front in the line of therapy for that particular patient population.

Trabectedin is a new agent that we"re using to treat patients with metastatic or advanced sarcomas, specifically liposarcoma and leiomyosarcoma. Patients with liposarcoma and leiomyosarcoma generally present with primary disease, although many patients present with metastatic disease. Patients who do present with metastatic disease are often treated with an anthracycline combination therapy such as doxorubicin plus dacarbazine or doxorubicin plus ifosfamide. That"s standard frontline therapy for patients with metastatic sarcoma for most types. There are certainly caveats and certainly situations where that"s not the case, but that is the usual course of action.

After an anthracycline-based therapy, patients with metastatic sarcoma are treated with second-line therapy. In the setting of a diagnosis of liposarcoma or leiomyosarcoma, those options are gemcitabine/docetaxel for leiomyosarcoma or trabectedin, which has activity and is now FDA approved for leiomyosarcoma but also for liposarcoma, including dedifferentiated and myxoid liposarcomas.

What important developments have occurred toward improving treatments in leiomyosarcoma?

Leiomyosarcoma, one of the more common subsets of soft tissue sarcomas, has been a focus of attention of at least two large phase III randomized trials recently completed, presented, and to be published soon. One of them would be the Yondelis trabectedin approval for patients with leiomyosarcoma. The other one is a drug called eribulin. Eribulin, similar to trabectedin, was tested in a randomized phase III trial against dacarbazine and the data presented at ASCO last year showed improvement in overall survival. The drug is not yet approved for this indication, but certainly the hope would be that that becomes part of the therapeutic armamentarium for patients specifically with leiomyosarcomas.

Patients diagnosed with metastatic leiomyosarcoma have been difficult to treat over the years. Standard regimens include a combination of an anthracycline such as doxorubicin plus dacarbazine, occasionally doxorubicin plus ifosfamide. Second-line therapy that has been used in the United States includes gemcitabine/docetaxel, and now we have a new agent, trabectedin, that has been proven to be effective in second- and third-line therapy for patients with leiomyosarcoma. This is based on a phase III study where patients with metastatic leiomyosarcoma and liposarcoma were randomized to either trabectedin or a comparator arm of dacarbazine. Trabectedin was found to be superior.

What important developments have occurred toward improving treatment in liposarcoma?

I think both the phase III trials that we just mentioned included patients with liposarcomas and leiomyosarcomas. Yondelis is now approved for use in the United States, as it was for many other parts of the world. Eribulin data, like I said, was presented at ASCO and showed survival advantage, but is not yet approved by the FDA for this indication.

Articles

Clinical Articles

Shreyaskumar R. Patel, MD and Jonathan C. Trent, MD discussed the use of trabectedin and the future of the treatment paradigms in soft tissue sarcoma.

Evolving Paradigms in STS: Perspectives With Shreyaskumar R. Patel and Jonathan C. Trent, MD

Currently, STS is difficult to treat due to its heterogeneity and the lack of available treatments. With advances in the knowledge of genetics, understanding of STS continues to increase. This increase of knowl- edge has promoted, and will continue to promote, the development of targeted therapies, which may aid in personalizing treatment and will help shape future standards of care.

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This section covers the Current Treatment Strategies section of the current Evolving Paradigms in Soft Tissue Sarcoma issue.

Evolving Paradigms in Soft Tissue Sarcoma: Conclusion and References

Cytotoxic chemotherapy is still one of the mainstays of treatment for patients with STS, yet several emerging agents are being investigated in STS and are making a difference in the treatment paradigm.

Aldoxorubicin is a prodrug of doxorubicin.

When administered intravenously, aldoxorubicin binds to albumin, which accumulates&nbsp;at solid tumors due to their high metabolic rate. In the acidic environment of the tumor, aldoxorubicin becomes the active drug, doxorubicin. This mechanism of delivery reduces the risk for cardiotoxicity, which is associated with doxorubicin. In the phase IIb trial, Chawla et al randomly assigned 83 patients with unresectable STS to receive aldoxorubicin 350 mg/m2 every 3 weeks and 40 patients to receive doxorubicin 75 mg/m2 every 3 weeks.

PFS was significantly longer with aldoxorubicin than doxorubicin (5.7 vs 2.8 months; P = .018). Common AEs included neutropenia, anemia, nausea, and mucositis. Aldoxorubicin was not associated with reduced left ventricular ejection fraction.

A new drug application is planned for aldoxorubicin as a second-line treatment for patients with relapsed STS, based on results from the phase III trial. Pre-NDA meetings have been arranged with the US FDA to discuss the application.

In the phase III trial, 433 patients with metastatic, locally advanced or unresectable STS who had not responded to or had progressed following a systemic regimen of non-adjuvant chemotherapy were randomized 1:1 to either aldoxorubicin or investigator&rsquo;s choice of chemotherapy regimens. The manufacturer reported that in 312 STS patients, aldoxorubicin demonstrated a significantly significant difference in PFS (

Aldoxorubicin showed a 38% reduction in risk of progression (HR, 0.62; 95% CI, 0.44-0.88). Overall, aldoxorubicin showed an improvement over investigator&rsquo;s choice of chemotherapy, but it did not reach statistical significance (HR, 0.81; 95% CI, 0.64-1.06;

= .012). AEs were similar to those noted in the phase IIb trial.

Evofosfamide, a DNA-alkylating agent also known as TH-302, is a prodrug that is activated in hypoxic environments. Because solid tumors have hypoxic regions, evofosfamide is more selective for tumor cells.

In a phase II study, 91 patients with advanced STS received evofosfamide 300 mg/m2 on days 1 and 8 and doxorubicin 75 mg/m2 on day 1 of each 21-day cycle.

Chawla et al found that PFS was 6.5 months. OS was 21.5 months, and 34% of patients had a PR. The study authors concluded that outcomes compared favorably with historical outcomes.&nbsp;

In the phase III SARC-021 trial by Tap et al, evofosfamide plus doxorubicin was compared with doxorubicin alone in patients with locally advanced unresectable or metastatic STS.

The authors concluded that the combination did not improve OS rates compared with doxorubicin alone (18.4 vs 19.0 months). The most common grade 3 to 5 AEs included anemia, neutropenia, and leucopenia. AEs led to death in 2.6% of patients in the combination arm and in 1% of patients in the doxorubicin alone arm.

Immunotherapy is increasingly being explored in STS, but has not yet been incorporated into standard practice.

Many researchers and ongoing trials are currently exploring the role of immunotherapy in the treatment of STS.

Pembrolizumab is one of the PD-1 inhibitors currently being investigated in sarcomas. In the phase II SARC-028 trial, pembrolizumab was studied both in pretreated patients with soft tissue and bone sarcomas.

Patients were treated with 200 mg of pembrolizumab every 3 weeks. Among the STS group, the ORR was 19% and the 4-month PFS rate was 44%. Common side effects included immune-related adrenal insufficiency, diarrhea, and acute interstitial nephritis.

Responses to pembrolizumab were greatest among patients with undifferentiated pleomorphic sarcoma. Among the 9 evaluable patients, the ORR was 44% including 4 patients with a PR and 3 patients with SD. As of 8 weeks, the PFS was 67%.

Among patients with leiomyosarcoma, none experienced a response, yet 6 patients had SD. The PFS rate at 8 weeks was 50%. Patients with synovial sarcoma experienced a PFS of 30%. Only 1 patient in this population experienced a PR and 2 had SD.  &nbsp;

Nivolumab, another PD-1 inhibitor, was also tested in 20 patients with metastatic STS and 3 patients with bone sarcomas. In the trial by Paoluzzi et al, patients received 3 mg/kg of nivolumab intravenously every 2 weeks with or without additional pazopanib at 800 mg daily.

Overall, clinical benefit was observed in 39% of the patients. Three patients experienced a PR, including 1 patient with proximal epithelioid sarcoma who also received pazopanib. Mixed responses were noted in 2 patients with STS and 4 patients with STS experienced SD. The most common side effects included grade 1 to 2 liver function transaminase elevation, especially among patients receiving the combination regimen, and grade 3 to 4 toxicities included elevated liver function transaminase levels, pneumonitis, colitis, and anemia.

An ongoing phase II trial is currently exploring combining nivolumab with or without the CTLA-4 inhibitor ipilimumab in patients with metastatic unresectable STS or bone sarcoma.

PD-L1 expression has shown potential in other tumor types to be predictive of responses to PD-1 inhibitors, such as pembrolizumab and nivolumab. In STS, PD-1 positive lymphocytes and PD-L1 expression could be used as a prognostic indicator, and has shown a correlation with reduced OS and event-free survival rates.

Testing patients for PD-L1 expression could be used to help select which patients would benefit more from treatment with a PD-1 inhibitor. Further, in the trial by Paoluzzi et al, the highest expression of PD-L1 was observed in those who experienced a PR.

Targets of therapy with activity in soft tissue sarcoma are depicted in

STS express factors for angiogenesis, such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF).

Such factors are required for the development of sarcomas. Activation of proto-oncogenes also aid in the development of sarcomas. The inhibition of tyrosine kinase receptors disrupts cell signaling and has demonstrated clinical benefit in gastrointestinal stromal tumors (GIST) with imatinib and sunitinib and in STS with pazopanib. Although imatinib and sunitinib are effective in GIST, they have not demonstrated activity in STS as a whole.

Sorafenib, an inhibitor of VEGF, is also not effective for STS.

Anlotinib is a multitarget RTK inhibitor, and in a phase II study in China, the progression-free response at 12 weeks was 57.23% and the median PFS was 5.63 months.

Anlotinib was particularly effective in patients with synovial sarcoma and alveolar soft part sarcoma. The most common grade 3 to 4 AEs included hypertension, pneumothorax, and thyroid hypofunction.

Regorafenib is a multikinase inhibitor, and in a phase II study, Mir et al found that regorafenib may have antitumor activity in non-adipocytic STS.

In 57 patients with leiomyosarcoma and 53 patients with other STS, regorafenib significantly improved PFS compared with placebo (4.0 vs 1.9 months, P = .017; 4.6 vs 1.0 months, P= .002, respectively).

At 6 months, rates of OS were better with regorafenib than placebo among patients with leiomyosarcoma (87% vs 75.9%, respectively; P = .013). In synovial sarcoma, regorafenib showed improved PFS over placebo (5.6 vs 1.0 months, respectively;

Whereas in adipocytic STS, PFS was better with placebo compared with regorafenib (1.7 vs 1.1 months, respectively). Improvements in OS rates were not deemed clinically relevant in the trial though due to crossover.

Mammalian target of rapamycin (mTOR), a kinase, participates in a pathway often deregulated in cancers.

Ridaforolimus, temsirolimus, and sirolimus inhibit mTOR, but benefits with therapy have been limited. In a phase II study, clinical benefit response rate with ridaforolimus was 28.8% among 212 patients with advanced STS or bone sarcomas. Median OS was 40 weeks and PFS was 15.3 weeks. AEs included stomatitis, mouth ulceration, rash, and fatigue. Researchers concluded that ridaforolimus has favorable survival benefits compared with historic metrics. In a phase III trial, ridaforolimus significantly improved PFS compared with placebo (17.7 vs 14.6 weeks), but OS with ridaforolimus was similar to placebo.

With temsirolimus, 39 out of 41 patients had disease progression and only 2 patients had a confirmed PR.

Median time to progression was 2 months. Radiographic response to sirolimus was observed in 3 patients with perivascular epithelioid cell tumors.

Similar to many tyrosine kinase receptor inhibitors, many monoclonal antibodies can target angiogenic factors. Bevacizumab, a recombinant human monoclonal antibody, binds VEGF. D&rsquo;Adamo et al evaluated the activity of bevacizumab with doxorubicin in 17 patients with metastatic STS.

They found that response rate (12%) with combination therapy was not higher than response rates with doxorubicin alone, but they did find that more than half of patients had SD for &ge;4 cycles.

Cixutumumab, a fully human monoclonal antibody, inhibits growth factor type 1 receptor and may be active in adipocytic sarcoma.

In a phase II study, patients with STS or Ewing family tumors received cixutumumab. At 12 weeks, the rate of PFS was greatest with adipocytic sarcoma compared with other STS. Ontuxizumab targets endosialin, which aids in the growth of tumor blood vessels.

Endosialin is usually expressed only by tumor cells. In an ongoing phase II study, researchers are evaluating the combination of ontuxizumab with gemcitabine and docetaxel in patients with metastatic STS.

Emerging Therapies for Specific Histiologies

Lesions of leiomyosarcoma have smooth muscle features and mainly occur in the retroperitoneum.

Some may occur in the large blood vessels. Along with liposarcoma, leiomyosarcoma is one of the most common STS subtypes, and response of leiomyosarcoma to cytotoxic therapy varies, especially in regards to tumor location. Uterine leiomyosarcoma has demonstrated response to gemcitabine with or without docetaxel.

In the TAXOGEM study, Pautier et al assigned 90 patients to receive either gemcitabine alone or with docetaxel. ORRs were 19% with gemcitabine and 20% with combination therapy among patients with uterine leiomyosarcomas. For nonuterine leiomyosarcomas, ORRs were 14% and 5%, respectively. The 3-month PFS rate was 40% for uterine and non-uterine leiomyosarcomas.

Criticisms of the study suggest that comparisons cannot be made between the study groups because the study is not appropriately powered.

The combination of temozolomide, bevacizumab, and cabozantinib (an inhibitor of MET and VEGF) demonstrated synergistic effects among 20 patients with heavily pretreated uterine leiomyosarcoma.

Gemcitabine with docetaxel at a fixed rate showed objective responses in 35.8% of patients with uterine leiomyosarcoma.

CRs were noted in 4.8% and PRs in 31%. The most common grade 3 to 4 AEs included neutropenia, anemia, fatigue, and thrombocytopenia. The median PFS was 4.4 months and the median OS was more than 16 months. In a larger study of patients with uterine leiomyosarcoma, also by Hensley et al, patients taking gemcitabine and docetaxel alone experienced a median PFS of 6.2 months and a median OS of 26.9 months.

Trabectedin improved responses in advanced uterine leiomyosarcoma over dacarbazine in a subgroup analysis of a phase III trial.

The PFS was increased (4.0 vs 1.5 months with trabectedin and darcarbazine, respectively) but OS was not significantly improved in this pretreated population (HR, 0.89;

= .5107). Risk of progression was reduced by 43%.

The most common liposarcoma is atypical lipomatous tumor/well-differentiated (ALT/WD) liposarcoma. ALT/WD liposarcoma usually occurs in the deep tissue of the extremities, especially the thigh, and is characterized&nbsp;by ring and giant rod chromosomes. Myxoid liposarcoma is the second most common liposarcoma and is composed of oval shaped cells. They usually occur in the extremities, and >90% of cases present with the translocation t(12;16)(q13;p11), which results in the fusion of FUSDDIT3.

Although exact mechanisms are unclear, trabectedin promotes the differentiation of myxoid tumors by interacting with FUSDDIT3.

This interaction may explain the response myxoid tumors have with trabectedin. Among 51 patients with myxoid liposarcoma, overall response to trabectedin was 51%, PFS rate was 88% at 6 months, and PFS was 14 months.

Grosso et al found similar results, with a 50% response rate per RECIST and a 17-month PFS.

As noted, trabectedin has recently been approved by the FDA for the treatment of both liposarcoma and leiomyosarcoma on the basis of phase III trial results.

is amplified in >90% of well-differentiated and dedifferentiated liposarcomas. The selective cyclin-dependent kinase 4/6 inhibitor palbociclib (PD0332991) was studied in a phase II study by Dickson et al.

At 12 weeks, the PFS was 66% and the median PFS was 18 weeks. Grade 3-4 AEs included anemia, thrombocytopenia, neutropenia, and febrile neutropenia. Palbociclib has been accepted as a treatment option for patients with well-differentiated or dedifferentiated liposarcoma for retroperitoneal sarcomas.

Eribulin has been compared with dacarbazine in 452 patients with liposarcoma and leiomyosarcoma. Patients receiving eribulin had an OS of 13.5 months compared with dacarbazine (11.5 months), but the difference was not significant (P = .017). PFS was also not significantly different between the 2 groups.

Alveolar soft part sarcomas (ASPS) are composed of large epithelioid cells organized in nests that are separated by thin blood vessels.

They mainly occur in the extremities and account for <1% of all STS.

Although diagnosis can occur at any age, median age of diagnosis is 30, which is younger than the age of diagnosis for STS in general. ASPS is associated with low rates of local and distant recurrence, and when metastasized, usually spreads to the lungs. It is also associated with brain metasteses.

Reported 5-year OS rates range from 50% to 85%.

This section covers the Emerging Cytotoxic Agents, Current and Emerging Targets, and Emerging Therapies for Specific Histologies sections of the current Evolving Paradigms in Soft Tissue Sarcoma issue.

Soft Tissue Sarcoma | Evolving Paradigms

Evolving Paradigms in STS: Perspectives With Shreyaskumar R. Patel and Jonathan C. Trent, MD

Evolving Paradigms in Soft Tissue Sarcoma: Conclusion and References

Evolving Paradigms in Soft Tissue Sarcoma: Current and Emerging Targets

Evolving Paradigms in Soft Tissue Sarcoma: Current Treatment Strategies

Evolving Paradigms in Soft Tissue Sarcoma: Introduction

Evolving Paradigms in STS: Perspectives With Shreyaskumar R. Patel, MD and Jonathan C. Trent, MD