Weijing Sun, MD, FACP, professor of medicine, The Sprint Professorship of Medicine Oncology, University of Kansas School of Medicine, director, Division of Medical Oncology, associate director, University of Kansas Cancer Center, discusses the design of the KEYNOTE-062 trial in advanced gastric/gastroesophageal junction (GEJ) cancer.

The randomized, phase 3 KEYNOTE-062 trial was a complex study that evaluated whether checkpoint inhibitors could be used in the frontline setting, as a single agent or in combination with chemotherapy, in patients with advanced gastric cancer, says Sun. Moreover, the analysis had a hierarchical design and consisted of 3 treatment arms. Patients were randomized 1:1:1 to receive pembrolizumab (Keytruda), pembrolizumab plus chemotherapy, or chemotherapy plus placebo. The primary end points of the trial were overall survival and progression-free survival in patients with PD-L1 combined positive score of 1 or greater, which was considered a noninferiority evaluation.

in September 2020, showed that among 763 enrolled patients with untreated, locally advanced/unresectable or metastatic gastric/GEJ cancer, pembrolizumab was noninferior to chemotherapy in terms of OS. Fewer adverse effects were also observed with the investigational regimen, Sun concludes.

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Weijing Sun, MD, FACP, discusses the design of the KEYNOTE-062 trial in advanced gastric/gastroesophageal junction cancer. 

Dr. Sun on the KEYNOTE-062 Design in Advanced Gastric/GEJ Cancer 

Jordan D. Berlin, MD, Ingram Professor of Cancer Research, professor of medicine, VICC associate director for clinical research strategy, director of the Phase I Program in Gastrointestinal Malignancies, Clinical Trials, in the Department of Medicine at Vanderbilt University Medical Center, discusses unmet needs in pancreatic cancer.

Historically, other than chemotherapy, the pancreatic cancer armamentarium has had limited treatment options available, says Berlin. Targeted therapy options, such as TRK inhibitors for patients with 

 fusions are available. Additionally, immunotherapy may be an option for patients with microsatellite instability–high disease. Patients with germline 

 mutations could be eligible to receive PARP inhibitors, Berlin explains. ​However, taken collectively, only around 5% of patients with pancreatic cancer are eligible for these targeted options, which spotlights the need for additional options. 

Future research efforts may focus on the utility of immunotherapy for patients in this setting. Furthermore, an emphasis will likely be placed on metabolism and evaluating additional agents that may inhibit DNA damage repair. Additionally, developing addition targeted therapies that inhibit more common mutations, such as 

, are relevant ongoing efforts, Berlin concludes.

Jordan D. Berlin, MD, discusses unmet needs in pancreatic cancer.  
  


Dr. Berlin on Unmet Needs in Pancreatic Cancer 

Sikander Ailawadhi, MD, professor of medicine, Division of Hematology/Oncology, Departments of Medicine and Cancer Biology, Mayo Clinic, discusses the emergence of T-cell engagers in multiple myeloma.

During the virtual 2020 ASH Annual Meeting & Exposition, data regarding bispecific antibodies and antibody-drug conjugates (ADCs), were presented. Moreover, MEDI2228, a BCMA-directed ADC, and AMG 701, a BCMA-directed bispecific T-cell engager, demonstrated encouraging early efficacy in relapsed/refractory multiple myeloma. Utilizing T-cell engager therapies in multiple myeloma may provide patients with deep, sustained responses and limited early toxicity, Ailawadhi explains.

Comparatively, CAR T-cell therapy is also emerging into the myeloma space, Ailawadhi explains. Although these data are maturing, the cellular therapy appears to induce deep, early responses that may not be sustained. As such, T-cell engagers could offer patients who progress after CAR T-cell therapy, along with those who are not candidates for CAR T-cell therapy, the opportunity to derive sustained responses without significant toxicity, concludes Ailawadhi. 

Sikander Ailawadhi, MD, discusses the emergence of T-cell engagers in multiple myeloma.  



Dr. Ailawadhi on the Emergence of T-Cell Engagers in Multiple Myeloma 

Phuong L. Mai, MD, a hematologist/oncologist at the University of Pittsburgh Medical Center Hillman Cancer Center, discusses barriers of genetic testing in colorectal cancer (CRC).

In CRC, access to genetic services continues to stand in the way of a more widespread use of genetic testing. Although patients in large cities likely have access to centers that offer genetic testing, patients in rural areas may have to travel 3 or 4 hours to the nearest center, says Mai. 

Additionally, physician and patient awareness of the importance of genetic testing remains a challenge, Mai says. Providers may not recognize when to refer patients to genetic services, and patients may become skeptical when they are recommended for genetic testing. 

Finally, the financial toxicity associated with genetic testing may be a barrier for some patients as their insurance may not cover the potentially prohibitive cost of testing, concludes Mai. 

Phuong L. Mai, MD, discusses barriers of genetic testing in colorectal cancer.  



Dr. Mai on Barriers of Genetic Testing in CRC 

Yi Lin, MD, PhD, consultant, Division of Hematology, Department of Internal Medicine, consultant, Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, assistant professor of medicine and oncology, Mayo Clinic, discusses CAR T-cell therapy–related toxicities in multiple myeloma.

In multiple myeloma, investigational CAR T-cell therapy products do not appear to induce the same degree of severe toxicities as in other hematologic malignancies, explains Lin. For example, as demonstrated in several clinical trials, less than 10% of patients typically develop grade 3 or higher cytokine release syndrome or neurotoxicity that would require monitoring in the intensive care unit, says Lin.

Notably, some contributing factors to this lesser degree of severe toxicities could be the design of the CAR T-cell products, along with the natural aspects of the disease. The field is now trying to gain a greater understanding on how to best utilize interventions, such as tocilizumab (Actemra) and steroids, to retain response while preventing severe toxicities, concludes Lin.

Yi Lin, MD, PhD, discusses CAR T-cell therapy–related toxicities in multiple myeloma.  



Dr. Lin on CAR T-Cell Therapy–Related Toxicities in Multiple Myeloma 

Ryan Sullivan, MD, medical oncologist, attending physician, Division of Hematology/Oncology, Massachusetts General Hospital, discusses treatment sequencing with targeted therapy and immunotherapy in melanoma. 

Typically, patients with advanced melanoma receive immunotherapy in the frontline setting, Sullivan explains. However, with the emergence of BRAF/MEK targeted therapies, the question remains whether targeted therapy or immunotherapy is the optimal frontline regimen, says Sullivan. Whether targeted therapy can replace single-agent PD-1 inhibitors or combination regimens with PD-1 and CTLA-4 inhibitors in this setting is unknown.

As such, treatment decisions should be made on an individualized basis in melanoma, Sullivan explains. Additionally, ongoing efforts are exploring how to optimize second-line treatment for patients who progress in the frontline setting. Few patients will retain long-term disease control with targeted therapy, single-agent immunotherapy, or combination immunotherapy, so additional advances are needed in this space, concludes Sullivan. 

Ryan Sullivan, MD, discusses treatment sequencing with targeted therapy and immunotherapy in melanoma.  



Dr. Sullivan on Sequencing Targeted Therapy and Immunotherapy in Melanoma 

Yelena Y. Janjigian, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the importance of routine HER2 testing in gastric/gastroesophageal (GEJ) cancer. 

Currently, routine HER2 testing is offered at most academic centers because first-line trastuzumab (Herceptin) is a standard of care for patients with HER2-positive metastatic gastric/GEJ cancer, Janjigian explains. However, in some areas of the world and in the community setting, HER2 testing is less widely available in this space. 

Notably, about 20% to 30% of patients with HER2-positive gastric/GEJ cancer will lose HER2 expression after they progress on first-line trastuzumab, Janjigian says. As such, routine HER2 testing is needed to inform the optimal second- and third-line therapy for patients. This becomes more relevant as more HER2-directed agents are introduced to the space, concludes Janjigian.

Yelena Y. Janjigian, MD, discusses the importance of routine HER2 testing in gastric/gastroesophageal cancer.  



Dr. Janjigian on the Importance of Routine HER2 Testing in Gastric/GEJ Cancer 

Rafael Fonseca, MD, interim director, Mayo Clinic Cancer Center, director, Innovation and Transformational Relationships, Mayo Clinic, discusses the emergence of minimal residual disease (MRD) in multiple myeloma.

Although the utility of MRD remains somewhat controversial in multiple myeloma, ClonoSEQ, a next-generation sequencing assay that evaluates MRD, was approved in September 2018 for patients with multiple myeloma or acute lymphoblastic leukemia. Additional methods for measuring MRD, such as EuroFlow and Mass Spectrometry, are currently under investigation in this space. 

However, despite this approval, how to best utilize MRD as a biomarker to inform treatment decisions remains a largely unanswered question in myeloma, Fonseca explains. In clinical practice, Fonseca says that routinely testing for MRD is important for patients who  complete transplants on day 100, as well as those who achieve deep and durable complete remissions. Moreover, it is important to discuss the results of MRD assessments with patients as those who are MRD negative appear to have a reduced risk of relapse compared with MRD-positive patients, concludes Fonseca.

Rafael Fonseca, MD, discusses the emergence of minimal residual disease in multiple myeloma.  



Dr. Fonseca on the Emergence of MRD in Multiple Myeloma 

Michael Schweizer, MD, a physician of the Seattle Cancer Care Alliance, assistant professor in the Division of Medical Oncology at the University of Washington School of Medicine, and associate professor in the Clinical Research Division at the Fred Hutchinson Cancer Research Center, discusses the results of the HERO trial in prostate cancer.

In the pivotal, phase 3 HERO trial, 934 patients with androgen-sensitive advanced prostate cancer were randomized 2:1 to receive 120 mg of oral relugolix (Orgovyx) once daily after a one-time 360 mg loading dose of relugolix or a 3-month depot injection of leuprolide (Lupron). 

 The results showed that 96.7% (95% CI, 94.9%-97.9%) of men treated with relugolix achieved and maintained castration through 48 weeks compared with 88.8% (95% CI, 84.6% to 91.8%) with leuprolide, translating to an absolute difference of 7.9% (95% CI, 4.1%-11.8%). As such, relugolix demonstrated noninferiority and superiority (

 < 0.0001) versus leuprolide. Notably, all key secondary end points favored relugolix versus leuprolide (

 < 0.0001) and patients had rapid recoveries of testosterone, Schweizer says. 

Although relugolix was associated with lower rates of major adverse cardiovascular events compared with leuprolide, the safety and tolerability profiles of the 2 agents were similar. Common adverse events for patients treated with relugolix or leuprolide were hot flash (54.3% vs 51.6%, respectively), fatigue (21.5% vs 18.5%), constipation (12.2% vs 9.7%), diarrhea (12.2% vs 6.8%), arthralgia (12.1% vs 9.1%), and hypertension (7.9% vs 11.7%), Schweizer concludes. 

Michael Schweizer, MD, discusses the results of the HERO trial in prostate cancer. 
  


Dr. Schweizer on the Results of the HERO Trial in Prostate Cancer 

Daniel J. DeAngelo, MD, PhD, institute physician, chief, Division of Leukemia, Dana-Farber Cancer Institute, professor of medicine, Harvard Medical School, discusses the utility of moxetumomab pasudotox-tdfk (Lumoxiti) in hairy cell leukemia (HCL).

In September 2018, the FDA approved moxetumomab pasudotox, a CD22-directed cytotoxin, for the treatment of adult patients with relapsed/refractory HCL who received at least 2 prior systemic therapies, including a purine nucleoside analog. Since the regulatory decision, moxetumomab pasudotox has been a utilized as a salvage therapy for patients with HCL. Moreover, the agent has demonstrated significant benefit for patients who have multiple relapses or short remissions, or do not respond to cladribine or pentostatin. In addition, this therapy can be administered in the outpatient setting, which has been beneficial during the coronavirus disease 2019 pandemic, DeAngelo explains.

As such, in clinical practice, moxetumomab pasudotox is typically reserved for patients who are refractory to nucleoside analogs, defined as having a remission duration of less than 12 months, as well as those who have relapsed disease and are not candidates for aggressive nucleoside analog therapy, DeAngelo concludes.

Daniel J. DeAngelo, MD, PhD, discusses the utility of moxetumomab pasudotox-tdfk in hairy cell leukemia. 


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