Alessandro Gronchi, MD, chair of Sarcoma Service, IRCCS Foundation National Cancer Institute, Milan, Italy, discusses ​the results of the ​phase 2 TRASTS trial in soft tissue sarcoma.

The international, prospective TRASTS study, which was presented during the 

 ​evaluated the utility of trabectedin (Yondelis) in combination with radiation therapy ​in patients with localized myxoid liposarcoma.

Prior data showed that trabectedin alone induced tumor shrinkage in 40% to 50% of patients in this population, Gronchi says. Additionally, radiation therapy ​alone induces tumor shrinkage in about 40% of patients.

Findings from the study showed that 53% of patients ​treated had tumor shrinkage ​with 10% or less viable tumor remaining​, says Gronchi.

​Additionally, ​30% of patients achieved a partial response and 70% achieved stable disease with the combination, ​Gronchi adds.

Ultimately, the combination of trabectedin and radiation therapy appears to be a feasible and well-tolerated regimen in patients with localized myxoid liposarcoma, Gronchi concludes.

Videos

Alessandro Gronchi, MD, discusses ​the results of the ​phase 2 TRASTS trial in soft tissue sarcoma.

Dr. Gronchi on the Results of the TRASTS Trial in Soft Tissue Sarcoma

Daniel H. Ahn, DO, an oncologist, internist, and assistant professor of medicine at Mayo Clinic, discusses the evolution of targetable alterations in colorectal cancer (CRC).

 G12D, which was used as a predictive biomarker for anti-EGFR monoclonal antibodies, was one of the only targetable alterations in CRC, says Ahn.

However, several additional driver mutations, including 

 V600E ​mutations, microsatellite instability–high status, and 

 fusions, have been discovered, ​Ahn says. Additionally, 

 non-​V600E mutations are currently under exploration ​as potential actionable alterations.

Currently, the majority of patients with CRC will benefit from targeted therapy, ​whereas approximately 50% to 60% of patients derived benefit from targeted therapy in the past, Ahn explains.

The role of targeted therapy continues to advance the CRC armamentarium, and, as such, ​the use of comprehensive next-generation sequencing panels is critical to ensure patients undergo the optimal course of therapy, Ahn concludes.

Daniel H. Ahn, DO, discusses the evolution of targetable alterations in colorectal cancer. 

Dr. Ahn on the Evolution of Targetable Alterations in CRC 

Brandon Mahal, MD, assistant professor of radiation oncology, assistant director of community outreach and engagement, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, discusses the potential role of race with regard to molecular disparities among men with prostate cancer. 

 findings from a retrospective analysis demonstrated a potential link between the incidence of prostate cancer and its associated mortality according to racial or ethnic background.

Although race is a social construct, it has many environmental and cultural influences that contribute to a patient’s molecular makeup, Mahal says. Factors such as diet, exercise, environmental exposures, location, and experiences with racism may drive underlying alterations. 

For example, those experiences could lead to more comorbid conditions or higher levels of cortisol, which may induce a molecular change in a patient’s genome, Mahal says.

As such, the findings suggest that more non-white men with prostate cancer should be included on clinical trials to inform molecular disparities between all patients and provide a more comprehensive understanding of the disease mechanisms, concludes Mahal.

Brandon Mahal, MD, discusses the potential role of race with regard to molecular disparities among men with prostate cancer.  


Dr. Mahal on the Potential Role of Race in Prostate Cancer Disparities

Monica L. Baskin, PhD, professor, Division of Preventive Medicine, vice chair for culture and diversity, Department of Medicine, associate director, Community Outreach and Engagement, O’Neal Comprehensive Cancer Center, The University of Alabama at Birmingham, discusses treatment considerations in prostate cancer. 

Treatment selection is based on a collaborative discussion with the patient and their family, Baskin says.

A number of patient factors including disease stage and grade, age, general health status, and tolerance of potential adverse effects are used to inform treatment selection, explains Baskin.

Currently, radiation therapy, surgery, hormone therapy, chemotherapy, and immunotherapy are available treatment options for men with prostate cancer, says Baskin. 

Additionally, eligible patients may be considered for active surveillance if they do not require immediate treatment, concludes Baskin.

Monica L. Baskin, PhD, discusses treatment considerations in prostate cancer.  


Dr. Baskin on Treatment Considerations in Prostate Cancer

Alan P. Z. Skarbnik, MD, a hematologist/oncologist with Novant Health, discusses factors to consider in selecting between BTK inhibitors in mantle cell lymphoma (MCL).

Currently, ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa) are approved for the treatment of patients with MCL who have received at least 1 prior line of therapy.

However, with no head-to-head data available, selecting between the 3 agents can be challenging, says Skarbnik. Moreover, all 3 agents have demonstrated similar efficacy and manageable safety profiles in patients with MCL. 

Although cross-trial comparison is discouraged, the duration of response (DOR) with acalabrutinib appears to be longer compared with ibrutinib, Skarbnik says. However, patients in the acalabrutinib clinical trial were not as heavily pretreated as those in the ibrutinib trial. The median number of prior lines of therapy was 2 and 3, respectively.

Additionally, zanubrutinib has demonstrated good DOR and depth of response among patients with MCL, Skarbnik says.

Toxicity and tolerability may be key indications to guide which BTK inhibitor is best suited for a particular patient with MCL, concludes Skarbnik.

Alan P. Z. Skarbnik, MD, discusses factors to consider in selecting between BTK inhibitors in mantle cell lymphoma.  



Dr. Skarbnik on Selecting Between BTK Inhibitors in MCL 

Patients with MPNs can be separated into 2 different groups: There are those who have early disease with essential thrombocythemia and polycythemia vera (PV), where the management is focused on trying to decrease the risk of thrombosis and bleeding. Management strategies for these patients include theuse of aspirin, selective use of phlebotomy for patients with PV, cytoreduction with an interplay of hydroxyurea, pegylated interferon-a2 (PEG-IFNa2; Pegasys), and JAK inhibitors, such as ruxolitinib (Jakafi).

Patients with myelofibrosis, however, have more life-threatening conditions and tend to have a higher burden of disease with splenomegaly symptoms and cytopenias. They also have a much higher risk of disease-related mortality. There is a balance between the timing of stem cell transplantation and medical therapy. The field now has 2 approved therapies, ruxolitinib and fedratinib (Inrebic), with several other JAK inhibitors following close behind in the pipeline, including momelotinib (formerly GS-0387, CYT-387) and pacritinib. Other exciting new therapies and combinations are forthcoming, as well, concludes Mesa.

Ruben A. Mesa, MD, discusses management strategies for patients with myeloproliferative neoplasms.

Dr. Mesa on Management Strategies for MPNs

Farrukh Awan, MD, an associate professor in the Department of Internal Medicine at UT Southwestern Medical Center (UTSW), and a member of the Division of Hematology and Oncology at UTSW's Harold C. Simmons Comprehensive Cancer Center and William P. Clements Jr. University Hospital, discusses treatment options in the first relapsed setting in patients with chronic lymphocytic leukemia (CLL).

Treating patients with relapsed CLL depends on the therapy the patient has relapsed on, says Awan. Is it chemotherapy, a BTK inhibitor, or a BCL-2 inhibitor? With the current trials that are ongoing, the other considerations are whether the patient has had a time-limited option, if they were off treatment, or whether they relapsed while actively undergoing treatment. These are important factors to consider when talking about the treatment of patients in the relapsed setting.

Looking at chemoimmunotherapy specifically, a patient could have received bendamustine/rituximab (Rituxan); fludarabine plus cyclophosphamide and rituximab; or rituximab alone. If the patient has relapsed following chemoimmunotherapy, then it is an open discussion for next steps, similar to the untreated setting, adds Awan. A BCL-2 inhibitor or a BTK inhibitor can be used, though PI3K inhibitors should be avoided in this setting, Awan explains. Data suggest that acalabrutinib (Calquence) as a single agent may be more effective than the combination ofidelalisib (Zydelig) and rituximab.

If a patient cannot tolerate a BTK inhibitor, then that is a separate issue, Awan says. For those patients, another option is the BCL-2 inhibitor venetoclax (Venclexta). Time-limited duration and comorbid conditions all help make a decision between BCL-2 and BTK inhibitors in the first relapsed setting, concludes Awan.

Farrukh Awan, MD, discusses treatment options in the first relapsed setting in patients with chronic lymphocytic leukemia.

Dr. Awan on Treatment Options in the First Relapsed Setting of CLL

Arun Azad, PhD, an associate professor at Peter MacCallum Cancer Centre and the University of Melbourne; fellow at Victorian Cancer Agency; and chair of the ANZUP Cancer Trials Group Translational, discusses the significance of the PROfound trial in metastatic castration-resistant prostate cancer (mCRPC).

 evaluated the efficacy and safety of olaparib (Lynparza) versus abiraterone acetate (Zytiga) or enzalutamide (Xtandi) in patients with mCRPC who progressed on prior hormonal anticancer treatment and harbored 

Results showed that olaparib significantly improved overall survival compared with enzalutamide or abiraterone.

​Moreover, as an early example of ​the efficacy of precision medicine in ​men with prostate cancer, these data garnered significant excitement, Azad adds.

As such, several ongoing studies are now evaluating combinations with PARP inhibitors in earlier disease settings​, Azad says.

Ultimately, the PROfound study set the stage for precision medicine in the advanced prostate cancer space, Azad concludes.

Arun Azad, PhD, discusses the significance of the PROfound trial in metastatic castration-resistant prostate cancer. 

Dr. Azad on the Significance of the PROfound Trial in mCRPC

Philip W. Kantoff, MD, chair of the Department of Medicine at Memorial Sloan Kettering Cancer Center and a 2014 Giants of Cancer Care® winner for Genitourinary Cancer, discusses future research efforts in prostate cancer.

 provided the field of prostate cancer with an abundance of research with regard to novel treatment strategies.

​Other than PARP inhibitors, few treatment options ​are available for patients with prostate cancer who harbor DNA repair gene abnormalities, Kantoff explains. As such, the field is actively trying to improve PARP inhibition by evaluating these agents in combination with other therapies​, says Kantoff.

Additionally, ongoing research is evaluating BCL-2 inhibitors in combination with other agents​, Kantoff explains.

These investigational treatment strategies could have utility in men with prostate cancer ​pending further positive data, Kantoff concludes.

Philip W. Kantoff, MD, discusses future research efforts in prostate cancer.

Dr. Kantoff on Future Research Efforts in Prostate Cancer 

Neal D. Shore, MD, FACS, medical director, of the Carolina Urologic Research Center, discusses unmet needs in nonmetastatic castration-resistant prostate cancer (CRPC)​.

Historically, conventional imaging and bone scans yielded negative findings despite patients having rising prostate-specific antigen (PSA) and below castration-range testosterone levels, says Shore. 

Prior research demonstrated that rising PSA correlates with progressive disease by way of bone metastasis, soft tissue lymph node involvement, and visceral metastasis of the lung or liver, Shore says.

Additionally, until the phase 3 ARAMIS trial, there was limited level 1 evidence to suggest which therapies could delay the progression of positive findings on imaging, concludes Shore.

Neal D. Shore, MD, FACS, discusses unmet needs in nonmetastatic castration-resistant prostate cancer.

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