
Denise Myshko is your editorial contact for the Oncology Business Management section of 

, as well as the corporate newsletters. She joined 

 in March 2020. Before that, she was managing editor of PharmaVOICE, a trade publication in the pharmaceutical industry. Email: 

Treatment approaches are being refined by the primary location of gastroesophageal junction (GEJ) tumors, said Stephen C. Yang, MD, during the 

“The site does matter because it influences therapy,” said Yang, associate vice chair for faculty development, and professor of surgery and medical oncology at Johns Hopkins University School of Medicine in Baltimore, Maryland. “A multidisciplinary approach remains necessary for all of these tumors. It not only involves the esophageal group but also the gastric group at our institution.”

But Yang said there has been confusion about whether junction tumors should be treated as esophageal or gastric cancer. The confusion, he said, could be related to the fact that there are several ways to classify these tumors.

Classifying a Tumor: Gastric or Esophageal

The most commonly used classification for assessing and planning treatment of GEJ tumors is the Siewert classification, which has been used since the 1980s.

 Type I is similar to esophageal cancers by epidemiology and histology and type III is similar to distal gastric tumors with intestinal and diffuse histologic types and no association with reflux, Yang said. Type I GEJ tumors are 1 to 5 centimeters above the GEJ with type III starting 2 cm below the junction. Type II tumors begin 1 cm above the junction to 2 cm below the junction (

Less commonly used systems, Yang said, are the Union for International Cancer Control and Nishi’s Japanese Classification of Esophageal Cancer.

Yang noted in his presentation that the National Comprehensive Cancer Network had adopted the Siewert classification. The guidelines describe Siewert types I and II tumors as being esophageal and suggests clinicians follow recommendations for esophageal cancer. Siewert type III tumors are described as gastric cancer.

Yang suggested clinicians consider the molecular and genomic classifications, especially for gastroesophageal adenocarcinoma, which is the primary histologic cell type in GEJ tumors. He pointed to a recent study

 that found similarities between adenocarcinomas of the stomach and esophagus and their definitive distinction from squamous cell carcinomas of the esophagus. The authors suggest that a “single-target, single-drug” rationale has proved too simplistic for GEJ adenocarcinoma because of the genomic instability and heterogeneity of this disease.

“The gastroesophageal junction tumors are [characterized by] mostly chromosomal instability but also share other genomic characteristics similar to gastric cancer but are still primarily associated with esophageal cancer,” Yang said. “A small component has genomic stable types that have microsatellite instability and also a small percentage are associated with the Epstein-Barr virus.”

Table. Siewert Classification of Gastroesophageal Junction Tumors

“No trials have specifically addressed this for true type II GEJ tumors,” he said. Yang said that the histology of the stomach away from the tumor may be the key to determining which classification these borderline tumors fall under. It’s important to determine if the rest of the mucosa is healthy, noted Yang. If there is atrophy of the mucosa, the presence of 

, or the patient has a history of reflux, it likely that the tumor is primarily gastric cancer. On the other hand, if the mucosa is healthy and there is 

Another controversy, Yang said, is the surgical approach and whether surgery should take more of the esophagus or more of the stomach. He cited a 2015 study, a retrospective analysis of 266 patients with surgically resectable GEJ adenocarcinomas from 2003 to 2013.

 The analysis reported that a positive circumferential resection margin was more common with gastrectomy (29%) versus esophagectomy (11%; 

 = .025). Further, no significant differences in mortality, morbidity, or disease recurrence were found.

Yang said another question that remains is whether to use induction or adjuvant radiation. A retrospective data analysis from the Surveillance, Epidemiology, and End Results registry database showed that adjuvant radiation therapy was associated with a survival benefit as compared with neoadjuvant radiation therapy for the treatment of patients with type II GEJ cancer.

A total of 1497 patients with resectable GEJ cancer were identified, with 746 receiving adjuvant radiation therapy and 751 receiving neoadjuvant radiation therapy.

Adjuvant radiation had a significantly lower death risk (HR, 0.84; 95% CI, 0.73-0.97; 

 = .0168) as well as a significantly lower disease-specific death risk (HR, 0.84; 95% CI, 0.72-0.97; 

“The individualized surgical approach remains critical not only preoperatively but also intraoperatively for decision making,” Yang said.

Curtis N, Noble F, Bailey I, Kelly JJ, Byrne JP, Underwood TJ. The relevance of the Siewert classification in the era of multimodal therapy for adenocarcinoma of the gastro-oesophageal junction. 

 2013;109(3):202-207. doi:10.1002/jso.23484           

National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Esophageal and esophagogastric junction cancers (version 1.2020). Accessed April 20, 2020. https:// www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf

Nagaraja A, Kikuchi O, Bass A. Genomics and targeted therapies in gastroesophageal adenocarcinoma. 

. 2019;9(12):1656-1672. doi:10.1158/2159-8290.CD-19-0487

Parry K, Haverkamp L, Bruijnen R, et al. Surgical treatment of adenocarcinomas of the gastro-esophageal junction. 

. 2015;22(2):597-603. doi:10.1245/s10434-014-4047-1

Miccio J, Oladeru O, Yang J. et al. Neoadjuvant vs. adjuvant treatment of Siewert type II gastroesophageal junction cancer: an analysis of data from the surveillance, epidemiology, and end results (SEER) registry.

. 2016;7(3):403- 410. doi:10.21037/jgo.2015.10.06

Yang said the variability of GEJ tumors has made treatment challenging. Controversies for GEJ tumors include the following: how best to stage these tumors, should induction or radiation be added to the regimen, what is the best surgical approach, and whether to add adjuvant therapies and under which situations.

Articles

Treatment approaches are being refined by the primary location of gastroesophageal junction tumors.

Primary Location of GEJ Tumors Affects Treatment

) meeting.

“The site does matter because it influences therapy,” said Yang, associate vice chair for faculty development, and professor of surgery and medical oncology at Johns Hopkins University School of Medicine in Baltimore, Maryland. “A multidisciplinary approach remains necessary for all of these tumors. It not only involves the esophageal group but also the gastric group at our institution.”

But Yang said there has been confusion about whether junction tumors should be treated as esophageal or gastric cancer. The confusion, he said, could be related to the fact that there are several ways to classify these tumors.





The most commonly used classification for assessing and planning treatment of GEJ tumors is the Siewert classification, which has been used since the 1980s.

).

Less commonly used systems, Yang said, are the Union for International Cancer Control and Nishi’s Japanese Classification of Esophageal Cancer.

Yang noted in his presentation that the National Comprehensive Cancer Network had adopted the Siewert classification. The guidelines describe Siewert types I and II tumors as being esophageal and suggests clinicians follow recommendations for esophageal cancer. Siewert type III tumors are described as gastric cancer.



Yang suggested clinicians consider the molecular and genomic classifications, especially for gastroesophageal adenocarcinoma, which is the primary histologic cell type in GEJ tumors. He pointed to a recent study

 that found similarities between adenocarcinomas of the stomach and esophagus and their definitive distinction from squamous cell carcinomas of the esophagus. The authors suggest that a “single-target, single-drug” rationale has proved too simplistic for GEJ adenocarcinoma because of the genomic instability and heterogeneity of this disease.

“The gastroesophageal junction tumors are [characterized by] mostly chromosomal instability but also share other genomic characteristics similar to gastric cancer but are still primarily associated with esophageal cancer,” Yang said. “A small component has genomic stable types that have microsatellite instability and also a small percentage are associated with the Epstein-Barr virus.”

Yang said the variability of GEJ tumors has made treatment challenging. Controversies for GEJ tumors include the following: how best to stage these tumors, should induction or radiation be added to the regimen, what is the best surgical approach, and whether to add adjuvant therapies and under which situations.



Another controversy, Yang said, is the surgical approach and whether surgery should take more of the esophagus or more of the stomach. He cited a 2015 study, a retrospective analysis of 266 patients with surgically resectable GEJ adenocarcinomas from 2003 to 2013.4 The analysis reported that a positive circumferential resection margin was more common with gastrectomy (29%) versus esophagectomy (11%; 

 = .025). Further, no significant differences in mortality, morbidity, or disease recurrence were found.

Yang said another question that remains is whether to use induction or adjuvant radiation. A retrospective data analysis from the Surveillance, Epidemiology, and End Results registry database showed that adjuvant radiation therapy was associated with a survival benefit as compared with neoadjuvant radiation therapy for the treatment of patients with type II GEJ cancer.



A total of 1497 patients with resectable GEJ cancer were identified, with 746 receiving adjuvant radiation therapy and 751 receiving neoadjuvant radiation therapy.

Adjuvant radiation had a significantly lower death risk (HR, 0.84; 95% CI, 0.73-0.97; 



“The individualized surgical approach remains critical not only preoperatively but also intraoperatively for decision making,” Yang said.

 2013;109(3):202-207. doi:10.1002/jso.23484

The need to adapt effectively and provide consistent care to patients with cancer during the public health threat caused by coronavirus disease 2019 (COVID-19) has prompted the expanded use of telehealth. Regulations on telehealth have been relaxed, and this affords oncology practices the opportunity to better serve this high-risk patient population during the COVID-19 crisis while mitigating the spread of the pandemic.

“Circumstances on the ground have radically changed in a short period of time where we recognize that telehealth technologies can be used in a public health emergency,” Ryan Howe, deputy director of the Hospital and Ambulatory Policy Group at the Centers for Medicare & Medicaid Services (CMS), said during a webinar on April 3, 2020, hosted by the Community Oncology Alliance (COA).

“We’ve really had to think strategically about how to manage [patients with cancer],” said Debra Patt, MD, MPH, MBA, a breast cancer specialist and executive vice president of Texas Oncology in Austin. “We cannot really stop operations…and if patients do not receive therapy for the months that we expect coronavirus to persist in our community, then their cancer will progress, and they will have an adverse outcome.”

Telehealth has enabled practices such as Texas Oncology to dramatically reduced clinic volumes, creating a safer environment for patients who still require treatment administered at health care facilities. “We have a desire to decrease the volume in our clinic by a large margin. By taking out all the follow-up patients, we were able to reduce our volume by 80%, making it a safer environment for our most vulnerable patients,” Patt said.

Telemedicine also gives clinics the opportunity for family consultations and important conversations about patients’ prognoses and whether they need advanced-care planning.

“With a patient with advanced cancer, this conversation is urgent, but you can’t have other people in the clinic now,” Patt said. “We have had to think strategically about how to manage patients. By reducing volume, we’ve created a safer environment that allows patients to get the care they need.”

Before the pandemic, statutory provisions limited the use of telehealth services that Medicare would cover. Patients had to live in a designated rural area and could access telehealth only in a health care setting (as opposed to their homes), and physicians had to be licensed in the state in which the patient resided.

 Because of such limitations, telehealth had little uptake prior to the pandemic, particularly among oncology practices.

Although more than 50 US health systems already had in place telehealth technology to allow clinicians to see patients at their home, few oncologists had embraced the technology.

On March 17, 2020, CMS waived the setting of care and geographic restrictions that had been place. By expanding this benefit on a temporary and emergency basis under the Coronavirus Preparedness and Response Supplemental Appropriations Act,

 CMS has authorized Medicare to pay for office, hospital, and other visits furnished via telehealth across the country, including in the patient’s home. The action, however, does not mean that state or local licensure is automatically waived; the American Medical Association (AMA) advises practices to check state requirements.

CMS is allowing licensed providers to render services outside their state of enrollment as well. The agency has indicated these are temporary waivers for the COVID-19 crisis, although several speakers at the COA webinar have indicated they would like to see these changes persist.

“CMS has been incredibly responsive. They have listened to what we have said and what we have asked for in terms changes for telehealth. Telehealth has been a virtual lifeline,” said Ted Okon, executive director at COA, said during the webinar.

Additionally, the Office for Civil Rights at the US Department of Health & Human Services said it would not impose penalties for noncompliance with requirements related to the Health Insurance Portability and Accountability Act (HIPAA) during the COVID-19 public health emergency.

 Some of the technologies being used for telehealth may not fully comply with the requirements of the HIPAA rules.

Private payers have followed CMS’ lead and made changes to their policies as well. The American Society of Clinical Oncology (ASCO) has put together a guide with information and updates about payers’ changes.

 Payers listed in ASCO’s guideline have issued temporary changes to their coverage for telehealth services. For example, they may waive member cost sharing for a covered telemedicine service or allow providers to bill for a standard face-to-face visit for all virtual care services, including those not related to COVID-19.

On April 30, CMS released an updated rule increasing payments for some visits via telehealth.

 In response to requests from ASCO, CMS is increasing payments for telephone evaluation and management visits to match payments for similar office and outpatient visits, which will increase payments from a range of about $14 to $41 to about $46 to $110. The payments are retroactive to March 1, 2020.

The AMA has developed a step-bystep guide to implementing telehealth based on insights from across the medical community,

 although the guide stresses that the process is not always straightforward. Licensure and reimbursement are 2 of the most common challenges to scaling telehealth in practice, and the AMA suggests that investing time in understanding the complexities will save time and resources later.

Speakers at COA’s webinar offered insight into their telehealth initiatives. For example, Texas Oncology, with 221 sites throughout the state and about 60,000 new patients a year, has been using telemedicine for 5 years, but because of statutory limitations, this was primarily a clinic-to-clinic operation, Patt said.

“We’ve previously used telemedicine to bridge the gaps in medical subspecialties and that is meaningful, but its use case was limited,” she said.

Texas Oncology began expanding its telemedicine services in February 2020. The first phase was to onboard about 15% of the clinicians to complement triage for acute care evaluations.

The second phase started in March, with onboarding for about 80% of clinicians for acute care, established visits, and new patient consultations. By early April, Texas Oncology had 500 doctors, 150 advanced practice providers, and 900 support staff who had access to the telemedicine program.

Patt said she would like to see CMS expand coverage of telehealth for preventive services and would like the expanded services to be available throughout 2020.

“There is a discordant narrative regarding expected duration of illness for the pandemic. Some practices have been reluctant to adopt changes because this may last only a month. That is a limitation. If CMS had a policy allowing this to last for the year, it would facilitate adoption.”

Bud Pierce, MD, PhD, a physician with Oregon Oncology Specialists, noted that the loosening of CMS regulations has also enabled practices to innovate. “As a long-time practitioner, I love doing this now, and it’s so powerful to take into the future to take better care of our patients. Let’s use technology to be innovative. One of the main impediments to innovation in medicines is rules and laws. We need to be paid for the work we do,” he said.

Oregon Oncology Specialists, which has 4 sites (soon to be 7) and sees 3000 new patients a year, has used Zoom over the past few weeks to conduct follow-up visits with several older patients who were concerned about coming to the office. “We’re using Zoom because we weren’t doing any telemedicine before this. This was so much better than a phone visit. It’s important to see patients. You get so much more from that,” he said.

But Patt cautioned clinicians about using some technologies. “It’s great that CMS has allowed for the noncompliant platforms such as FaceTime, Skype, and Zoom during the health crisis, but these are not long-term solutions,” she noted. Texas Oncology is using the VSee telemedicine platform, which is encrypted and HIPAA compliant.

Dennis Zoet, chief business development officer at Cancer & Hematology Centers of Western Michigan, said his group is using Doxy.me because it is easy for patients and is HIPAA compliant.

“This is the right vendor for my practice right now; I don’t know if this is the right vendor for my practice 6 months post- COVID-19 emergency implementation,” he said during the webinar.

Cancer & Hematology Centers of Western Michigan, which has 5 locations and saw 8000 new patients in 2019, was able to make telehealth available quickly. The practice signed up on March 18 and had the first virtual visit 2 days later. At the time of the webinar, 53 staff had been trained on the platform and the practice had 22 stations available for virtual visits, with 400 scheduled virtual visits.

Zoet offered a few lessons learned from his practice’s implementation, as well as points to consider. After 1 patient came to the office instead of doing a virtual visit and other patients said they did not have a usable or charged device, he implemented a training program for appointment schedulers and included a script for them to follow when speaking with patients.

“The patients are so appreciative, they are enjoying it, although they are experiencing some hiccups,” he said. “We also are doing quick surveys of 5 minutes to get feedback from the doctors and we have support for them as well.”

Mission Cancer & Blood in Des Moines, Iowa, is having nurses set up the telehealth appointments.

“The appointment scheduler is not a clinical person, and to now explain to the patient why we are switching them to a telehealth visit is a clinical discussion,” said Phil Stover, JD, MBA, the practice’s CEO. “We wanted this to be a clinical team assuring the patient we are taking care of them. That has helped us with streamlining the implementation.”

Mission Cancer & Blood, which has 3 main locations, also created a handbook for its providers with policies and procedures; information about One Touch Telehealth, the platform they are using; troubleshooting information; and how-to’s for engaging patients.

Medicare telemedicine health care provider fact sheet. Centers for Medicare and Medicaid Services website. Published March 17, 2020. Accessed April 15, 2020. https://go.cms.gov/3eIDPtH           

COVID-19 emergency declaration blanket waivers for health care providers. . Centers for Medicare and Medicaid Services website. Published April 21, 2020. Accessed April 29, 2020. https://www.cms.gov/files/document/summary-covid-19-emergency-declaration-waivers.pdf

Hollander JE, Carr BG. Virtually perfect? Telemedicine for covid-19 [published online March 11, 2020]. 

Cancer care goes virtual in response to covid-19 [published online April 10, 2020]. 

Telehealth implementation playbook. American Medical Association website. Updated April 23, 2020. Accessed April 28, 2020. https://bit.ly/35bc88s

Notification of enforcement discretion for telehealth remote communications during the COVID-19 nationwide public health emergency. US Department of Health and Human Services. Published March 30, 2020. Accessed April 16, 2020. https://bit.ly/2y9LbpN

Private payers: telemedicine and telehealth. American Society of Clinical Oncology website. Updated April 6, 2020. Accessed April 15, 2020. https://bit.ly/3cUk28V

Trump administration issues second round of sweeping changes to support US healthcare system during COVID-10 pandemic. CMS website. Published April 30, 2020. Accessed May 1, 2020. https://go.cms.gov/2LognvS

The need to adapt effectively and provide consistent care to patients with cancer during the public health threat caused by coronavirus disease 2019 has prompted the expanded use of telehealth.

Community Oncology Practices Offer Telehealth Tips

The need to adapt effectively and provide consistent care to patients with cancer during the public health threat caused by coronavirus disease 2019 (COVID-19) has prompted the expanded use of telehealth. Regulations on telehealth have been relaxed, and this affords oncology practices the opportunity to better serve this high-risk patient population during the COVID-19 crisis while mitigating the spread of the pandemic.

“Circumstances on the ground have radically changed in a short period of time where we recognize that telehealth technologies can be used in a public health emergency,” Ryan Howe, deputy director of the Hospital and Ambulatory Policy Group at the Centers for Medicare & Medicaid Services (CMS), said during a webinar on April 3, 2020, hosted by the Community Oncology Alliance (COA).

“We’ve really had to think strategically about how to manage [patients with cancer],” said Debra Patt, MD, MPH, MBA, a breast cancer specialist and executive vice president of Texas Oncology in Austin. “We cannot really stop operations…and if patients do not receive therapy for the months that we expect coronavirus to persist in our community, then their cancer will progress, and they will have an adverse outcome.”

Telehealth has enabled practices such as Texas Oncology to dramatically reduced clinic volumes, creating a safer environment for patients who still require treatment administered at health care facilities. “We have a desire to decrease the volume in our clinic by a large margin. By taking out all the follow-up patients, we were able to reduce our volume by 80%, making it a safer environment for our most vulnerable patients,” Patt said.

Telemedicine also gives clinics the opportunity for family consultations and important conversations about patients’ prognoses and whether they need advanced-care planning.

“With a patient with advanced cancer, this conversation is urgent, but you can’t have other people in the clinic now,” Patt said. “We have had to think strategically about how to manage patients. By reducing volume, we’ve created a safer environment that allows patients to get the care they need.”





Before the pandemic, statutory provisions limited the use of telehealth services that Medicare would cover. Patients had to live in a designated rural area and could access telehealth only in a health care setting (as opposed to their homes), and physicians had to be licensed in the state in which the patient resided.

 Because of such limitations, telehealth had little uptake prior to the pandemic, particularly among oncology practices.

Although more than 50 US health systems already had in place telehealth technology to allow clinicians to see patients at their home, few oncologists had embraced the technology.



On March 17, 2020, CMS waived the setting of care and geographic restrictions that had been place. By expanding this benefit on a temporary and emergency basis under the Coronavirus Preparedness and Response Supplemental Appropriations Act,2 CMS has authorized Medicare to pay for office, hospital, and other visits furnished via telehealth across the country, including in the patient’s home. The action, however, does not mean that state or local licensure is automatically waived; the American Medical Association (AMA) advises practices to check state requirements.



CMS is allowing licensed providers to render services outside their state of enrollment as well. The agency has indicated these are temporary waivers for the COVID-19 crisis, although several speakers at the COA webinar have indicated they would like to see these changes persist.

“CMS has been incredibly responsive. They have listened to what we have said and what we have asked for in terms changes for telehealth. Telehealth has been a virtual lifeline,” said Ted Okon, executive director at COA, said during the webinar.

Additionally, the Office for Civil Rights at the US Department of Health & Human Services said it would not impose penalties for noncompliance with requirements related to the Health Insurance Portability and Accountability Act (HIPAA) during the COVID-19 public health emergency.

 Some of the technologies being used for telehealth may not fully comply with the requirements of the HIPAA rules.

Private payers have followed CMS’ lead and made changes to their policies as well. The American Society of Clinical Oncology (ASCO) has put together a guide with information and updates about payers’ changes.

 In response to requests from ASCO, CMS is increasing payments for telephone evaluation and management visits to match payments for similar office and outpatient visits, which will increase payments from a range of about $14 to $41 to about $46 to $110. The payments are retroactive to March 1, 2020.





The AMA has developed a step-bystep guide to implementing telehealth based on insights from across the medical community,

Speakers at COA’s webinar offered insight into their telehealth initiatives. For example, Texas Oncology, with 221 sites throughout the state and about 60,000 new patients a year, has been using telemedicine for 5 years, but because of statutory limitations, this was primarily a clinic-to-clinic operation, Patt said.

“We’ve previously used telemedicine to bridge the gaps in medical subspecialties and that is meaningful, but its use case was limited,” she said.

Texas Oncology began expanding its telemedicine services in February 2020. The first phase was to onboard about 15% of the clinicians to complement triage for acute care evaluations.

The second phase started in March, with onboarding for about 80% of clinicians for acute care, established visits, and new patient consultations. By early April, Texas Oncology had 500 doctors, 150 advanced practice providers, and 900 support staff who had access to the telemedicine program.

Patt said she would like to see CMS expand coverage of telehealth for preventive services and would like the expanded services to be available throughout 2020.

“There is a discordant narrative regarding expected duration of illness for the pandemic. Some practices have been reluctant to adopt changes because this may last only a month. That is a limitation. If CMS had a policy allowing this to last for the year, it would facilitate adoption.”

Bud Pierce, MD, PhD, a physician with Oregon Oncology Specialists, noted that the loosening of CMS regulations has also enabled practices to innovate. “As a long-time practitioner, I love doing this now, and it’s so powerful to take into the future to take better care of our patients. Let’s use technology to be innovative. One of the main impediments to innovation in medicines is rules and laws. We need to be paid for the work we do,” he said.

Oregon Oncology Specialists, which has 4 sites (soon to be 7) and sees 3000 new patients a year, has used Zoom over the past few weeks to conduct follow-up visits with several older patients who were concerned about coming to the office. “We’re using Zoom because we weren’t doing any telemedicine before this. This was so much better than a phone visit. It’s important to see patients. You get so much more from that,” he said.

But Patt cautioned clinicians about using some technologies. “It’s great that CMS has allowed for the noncompliant platforms such as FaceTime, Skype, and Zoom during the health crisis, but these are not long-term solutions,” she noted. Texas Oncology is using the VSee telemedicine platform, which is encrypted and HIPAA compliant.

Dennis Zoet, chief business development officer at Cancer & Hematology Centers of Western Michigan, said his group is using Doxy.me because it is easy for patients and is HIPAA compliant.

“This is the right vendor for my practice right now; I don’t know if this is the right vendor for my practice 6 months post- COVID-19 emergency implementation,” he said during the webinar.

Cancer & Hematology Centers of Western Michigan, which has 5 locations and saw 8000 new patients in 2019, was able to make telehealth available quickly. The practice signed up on March 18 and had the first virtual visit 2 days later. At the time of the webinar, 53 staff had been trained on the platform and the practice had 22 stations available for virtual visits, with 400 scheduled virtual visits.

Zoet offered a few lessons learned from his practice’s implementation, as well as points to consider. After 1 patient came to the office instead of doing a virtual visit and other patients said they did not have a usable or charged device, he implemented a training program for appointment schedulers and included a script for them to follow when speaking with patients.

“The patients are so appreciative, they are enjoying it, although they are experiencing some hiccups,” he said. “We also are doing quick surveys of 5 minutes to get feedback from the doctors and we have support for them as well.”

Mission Cancer & Blood in Des Moines, Iowa, is having nurses set up the telehealth appointments.

“The appointment scheduler is not a clinical person, and to now explain to the patient why we are switching them to a telehealth visit is a clinical discussion,” said Phil Stover, JD, MBA, the practice’s CEO. “We wanted this to be a clinical team assuring the patient we are taking care of them. That has helped us with streamlining the implementation.”

Mission Cancer & Blood, which has 3 main locations, also created a handbook for its providers with policies and procedures; information about One Touch Telehealth, the platform they are using; troubleshooting information; and how-to’s for engaging patients.

Medicare telemedicine health care provider fact sheet. Centers for Medicare and Medicaid Services website. Published March 17, 2020. Accessed April 15, 2020. https://go.cms.gov/3eIDPtH

The armamentarium for patients with epithelioid sarcoma, a rare soft tissue sarcoma that primarily affects younger adults, now includes the novel targeted therapy tazemetostat (Tazverik). On January 23, 2020, the FDA granted an accelerated approval to the first-in-class EZH2 inhibitor, for the treatment of adult and pediatric patients 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.

The approval is based on findings from a cohort of patients with epithelioid sarcoma (cohort 5) in an ongoing, phase 2 study (EZH-202; NCT02601950). Investigators enrolled 62 patients with locally advanced or metastatic epithelioid sarcoma whose tumors lacked integrase interactor 1 (INI1) expression. Treatment with tazemetostat elicited an overall response rate of 15% (95% CI, 7%-26%), including a 1.6% complete response rate and a 13% partial response rate. Among the responders, 67% had a duration of response of at least 6 months (range, 3.7-24.5+).

“[Tazemetostat] is an advance over [other] treatments for epithelioid sarcoma because now we have a targeted therapy that has a mechanism and a biomarker,” Brian Van Tine, MD, PhD, said in an interview with 

. “We don’t usually talk about response rates in sarcoma, especially past first line. In general, this is a chemo-insensitive subset of sarcoma. The fact that there is a response rate is exciting.”

Epithelioid sarcoma is characterized by an aggressive behavior and a very poor prognosis, with metastases occurring in 30% to 50% of cases. Available treatment options have consisted primarily of anthracycline-based and gemcitabine-based chemotherapy, which have median progression-free survival rates of between 3 and 8 months.

Van Tine, an associate professor of medicine in the Division of Oncology, Section of Medical Oncology, at Washington University School of Medicine in St Louis and an investigator in the trial, discussed what the agent’s approval brings to the treatment landscape for this patient population.

Please provide an overview of the study that led to the approval of tazemetostat.

This was a multicenter, multicohort, phase 2, 7-arm study looking at different types of tumors. For example, there was a synovial sarcoma arm, an epithelioid sarcoma arm, [and] a rhabdoid tumor arm. Each of these had a biology that was predicted to respond to an EZH2 inhibitor. Two of the cohorts were for epithelioid sarcoma, with one of those requiring biopsies. There was an enrichment cohort once it was shown there was a signal to better understand the biology.

The biomarker that was used was loss of INI1 expression, which is part of the pathological workup for epithelioid sarcoma. This multiarm study, which provided a way of looking at many kinds of tumors, identified activity only in epithelioid sarcoma.

What is the mechanism of action of tazemetostat?

It is a small molecule EZH2 inhibitor. It is thought that the loss of INI1 would lead to increased EZH2 activity. There is large complex of chromatin remodeling proteins called SMARC. In the SMARC family, proteins come together to regulate chromatin modifications. One of those proteins is INI1. When you lose INI, you lose control of a protein called EZH2, which gets upregulated and starts modifying DNA. If you inhibit EZH2, the activity that is useful for cancer, you can get control of the chromatin modification in a way that tumors don’t like. You are driving a mechanism based on a loss of a protein that leads to upregulation of the protein.

The data cutoff was September 17, 2018. Patients with epithelioid sarcoma were treated with 800 mg of tazemetostat twice a day. They could have any line of prior treatment. There was a 15% partial response [rate] and a disease rate of 26%, but what was interesting is that the disease control rate was up to 103 weeks. The median overall survival in a chemo-insensitive type of sarcoma was 82 weeks. In general, compared with a lot of agents we use, this was relatively well tolerated. In terms of adverse [events], the biggest complaint was fatigue, nausea, and cancer pain.

Please discuss the other studies that are ongoing with tazemetostat.

We are currently participating in the phase 2 expansion, which is for patients who have already been treated. We are also participating in a phase 3 study [EZH-301; NCT04204941] that combines tazemetostat with doxorubicin. The expansion study is open label and open-ended. It gives patients access, but also, biologic data are being collected. The phase 3 trial is required by the FDA for continued approval. This is expected to be completed by 2029, and that is reflective of how rare this sarcoma is.

What are the recommendations for clinicians when using tazemetostat?

This is only for epithelioid sarcoma, and pathology should be confirmed. It’s important to match the drug to the right patient. Epithelioid sarcoma is a distinct sarcoma, and now there is a drug for it: Tazemetostat.

Tazverik. Package insert. Epizyme, Inc; 2020. Accessed April 13, 2020. www.accessdata.fda.gov/ drugsatfda_docs/label/2020/211723s000lbl.pdf           

Stacchiotti S, Schoffski P, Jones R, et al. Safety and efficacy of tazemetostat, a first-in-class EZH2 inhibitor, in patients (pts) with epithelioid sarcoma (ES) (NCT02601950). 

. 2019;37 (suppl 15):11003. doi:10.1200/JCO.2019.37.15_suppl.11003

Brian Van Tine, MD, PhD, discusses what tazemetostat’s approval brings to the treatment landscape for patients with epithelioid sarcoma.

Expert Explains Significance of Tazemetostat FDA Approval for Rare Sarcoma

Trametinib (Mekinist) monotherapy has emerged as a new treatment option for women with recurrent low-grade serous ovarian cancers based on improvements in survival outcomes and response rates demonstrated in a phase II/III study, according to David M. Gershenson, MD.

The findings involving the MEK inhibitor were scheduled to be presented at the 2020 Society of Gynecologic Oncology Annual Meeting on March 29 but were released electronically after the conference was canceled because of coronavirus disease 2019. In the NRG-GOG 0281 trial (NCT02101788), treatment with trametinib resulted in a 52% reduction in the risk of disease progression or death. The median progression-free survival (PFS) was 13.0 months (95% CI, 9.9-15.0) with trametinib compared with 7.2 months (95% CI, 5.6-9.9) for physician’s choice of standard-of-care (SOC) therapy (HR, 0.48; 95% CI, 0.36-0.64; 1-sided 

 <.0001). Median overall survival (OS) also was longer with trametinib therapy, but the results did not reach statistical significance.

“This was not only was the first study of trametinib in this patient population, but it also turned out to be the first positive randomized clinical trial of any targeted agent in low-grade serous carcinoma,” Gershenson, a professor of gynecologic oncology at The University of Texas MD Anderson Cancer Center in Houston, said in an interview with OncLive

. “It establishes trametinib as a new standard-of-care treatment option for women who have low-grade serous carcinoma.”

Low-grade serous carcinoma of the ovary or peritoneum is a rare subtype that comprises 5% to 10% of all serous cancers, Gershenson and colleagues said in their conference abstract. Most of these malignancies are diagnosed in advanced stages and more than 70% of those with stage II to IV disease will experience relapse.

Although chemotherapy and hormonal therapy are frequently administered to patients in the primary and recurrent disease settings

, low-grade serous carcinoma also is characterized by alterations in the MAP kinase cell-signaling network, which includes MEK proteins.

 Trametinib targets MEK 1/2 kinases and is given in combination with dabrafenib (Tafinlar), a BRAF inhibitor, in melanoma, non—small cell lung cancer, and anaplastic thyroid cancer metastases with BRAF V600 mutations.

In NRG-GOG 0281, patients were randomized 1:1 to be treated until progression with either trametinib at 2 mg daily or 1 of 5 SOC options: paclitaxel (80 mg/m

 weekly for 3 of 4 weeks), pegylated liposomal doxorubicin (40-50 mg on day 1 of 28-day cycle) , topotecan (4.0 mg/m

 weekly for 3 of 4 weeks), letrozole (2.5 mg daily), or tamoxifen (20 mg twice daily). Patients who progressed on SOC were allowed to cross over to trametinib . The primary end point was PFS; secondary objectives included OS, objective response rate (ORR), and toxicity.

In all, 260 patients with a median age of 56.2 years were enrolled between February 2014 and April 2018. The primary site of malignancy was the ovary for 90.8% of participants and the peritoneum for 9.2%. Overall, 48.1% had 3 or more prior lines of therapy. Median follow-up was 31.4 months.

In addition to a significant improvement in PFS, trametinib therapy also resulted in a higher response rate than SOC. The ORR was 26.2% (95% CI, 19.0%-34.0%) with trametinib versus 6.2% (95% CI, 2.0-10.0) with SOC, which translated into an odds ratio favoring trametinib of 5.4 (95% CI, 2.4-12.2; 

Response duration for those who received trametinib was longer compared with participants in the SOC arm; the median duration with trametinib was 13.6 months (95% CI, 8.1-18.8) versus 5.9 months (95% CI, 2.8-12.2) with SOC.

Additionally, median OS was 37.0 months (95% CI, 30.3-not estimable) with trametinib versus 29.2 months (95% CI, 23.5-51.6) with SOC, which represented a 25% reduction in the risk of death but not a statistically significant improvement (HR, 0.75; 95% CI, 0.51-1.11; 1-sided 

 = .054). The OS analysis in the SOC arm included patients who had crossed over to trametinib therapy after progressing on SOC. Among patients who crossed over (n = 88), the median PFS was 10.8 months (95% CI, 7.3-12.0), the ORR was 15% (95% CI, 7.0-22.0), and the duration of response was 15.9 months (95% CI, 4.2-22.1).

Treatment-emergent adverse events (AEs) were more prevalent in patients who received trametinib than in those in the SOC arm. Common all-grade AEs in the trametinib and SOC arms, respectively, were skin rash (92.1% vs 48.5%), fatigue (72.5% vs 57.8%), diarrhea (72.4% vs 33.6%), nausea (60.6% vs 50.8%), and anemia (51.9% vs 43.0%).

The principal toxicities of grade 3 or greater severity for trametinib versus SOC therapy, respectively, were hematologic (13.4% vs 9.4%), gastrointestinal (27.6% vs 29%), skin (15% vs 3.9%), and vascular (18.9% vs 8.6). AEs of special interest included decreased ejection fraction in 7.9% of patients who received trametinib compared with 0.8% with SOC and pneumonitis in 2.4% and 0% of patients, respectively. Among all participants, 35.4% in the trametinib arm discontinued treatment due to an AE or complication compared with 12.3% in the SOC arm.

“The MEK inhibitors can be tricky drugs to manage, and the [adverse] effects with trametinib are different from what you might see with conventional chemotherapy or endocrine therapies,” Gershenson said. “A number of patients in this trial did require dose reductions related to adverse events. It was moderately well tolerated but there are [adverse] effects clinicians need to be aware.”

Gershenson conducted this study of trametinib after an initial phase II study of patients with low-grade serous ovarian cancer treated with selumetinib, also a MEK1/2 inhibitor, demonstrated an ORR of 15% in this patient population. The FDA is reviewing selumetinib as a potential therapy for pediatric patients 3 years or older with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas.

“We knew that a drug that targeted the MAP pathway as MEK inhibitors do certainly had the potential benefit of helping patients,” Gershenson said. “There had also been preclinical work that showed that MEK inhibitors had activity in low-grade serous carcinoma cell lines, as well.”

Although trametinib is not FDA-approved ovarian cancer, the National Comprehensive Cancer Network (NCCN) added trametinib to the guidelines as an option for platinum-sensitive and platinum-resistant recurrent low-grade serous carcinoma after findings from NRG-GOG 0281 were presented at the 2019 European Society for Medical Oncology Annual Congress.

NRG Oncology in the United States and the National Cancer Research Network in the United Kingdom collaborated on the study.

Gershenson DM, Miller A, Brady W, et al. A randomized phase II/III study to assess the efficacy of trametinib in patients with recurrent or progressive low-grade serous ovarian or peritoneal cancer. For presentation at: 2020 Society of Gynecologic Oncology Annual Meeting; March 28-31, 2020; Toronto, Canada. Abstract 42. https://sgo.confex.com/sgo/2020/meetingapp.cgi/Paper/17159.

NCCN Clinical Practice Guidelines: ovarian cancer, including fallopian tube cancer and primary peritoneal cancer. Version 1.2020. National Comprehensive Cancer Network website. nccn.org/professionals/physician_gls/pdf/ovarian.pdf. Updated March 11, 2020. Accessed April 6, 2020.

Mekinist [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2019. www.accessdata.fda.gov/drugsatfda_docs/label/2019/204114s012lbl.pdf. Accessed April 6, 2020.

US FDA accepts regulatory submission for selumetinib in neurofibromatosis type 1 and grants priority review [press release]. Kenilworth, NJ: AstraZeneca and Merck & Co; November 14, 2019. bit.ly/2V6auAD. Accessed April 1, 2020.

Trametinib improves outcomes for women with low-grade serous carcinoma of the ovary/peritoneum on NRG Oncology trial. NRG Oncology website. bit.ly/3aQG5wH. Published September 29, 2019. Accessed April 6, 2020.

Trametinib monotherapy has emerged as a new treatment option for women with recurrent low-grade serous ovarian cancers based on improvements in survival outcomes and response rates demonstrated in a phase II/III study.

Trametinib Boosts PFS and Response Rates in Low-Grade Ovarian Cancer

Physicians treating patients with cancer may want to consider postponing surgeries or altering therapy plans because of the threat that the coronavirus (COVID-19) poses to this population, according to leading oncology experts. The evidence base to support best practices amidst the COVID-19 pandemic is both limited and evolving and several organizations have been working to provide access to the most up-to date resources.

Although the risk of COVID-19 to cancer patients is unknown, the potential threat of COVID-19 to immunocompromised patients as a result of their disease or the treatment is thought to be significant.

 Early published reports from China on the outcomes of patients with cancer infected with COVID-19 indicated 3.5 times higher risk of mechanical ventilation, ICU admission, or death compared with patients without cancer.

In the United States, there have been over 7000 confirmed cases of COVID-19, with over 100 deaths.

 According to the Centers for Disease Control and Prevention (CDC), most COVID-19 illness is mild, but a recent study out of China suggests serious illness occurs in 16% of cases. Older people and those with severe chronic medical conditions—such as heart disease, lung disease and diabetes&mdash;seem to be at higher risk of developing serious COVID-19 illness.

“Oncology professionals will play a vital role in caring for individuals who are particularly vulnerable to COVID-19,” Marcus Neubauer, MD, chief medical officer for The US Oncology Network told 

 in an email. “These patients will continue to need treatment for cancer or blood disorders, yet they may also present symptoms of the novel viral infection.”

In a soon-to-be-released paper, experts from the Seattle Cancer Care Alliance (SCCA)—of the National Comprehensive Cancer Network (NCCN)&mdash;share advice to oncology care physicians on how to provide optimal cancer care during the COVID-19 pandemic. The authors highlight the importance of organizational structure, preparation, agility, and a shared vision for continuing to provide cancer treatment to patients in the face of uncertainty and rapid change.

“Responding quickly and confidently to the COVID-19 crisis is the healthcare challenge of our generation,” F. Marc Stewart, MD, medical director, SCCA, said in a press release. “Our overarching goal is to keep our cancer patients and staff safe while continuing to provide compassionate, high-quality care under circumstances we’ve never had to face before.”

In a section concerning treatment decisions the SCCA recommends that for patients with solid tumors the adjuvant therapy with curative intent should proceed. In terms of scheduled surgical procedures, the panel states that while cancer-related surgery is not considered “elective” and does not fall under the guidance for a ban on elective procedures, interventions should be prioritized. For example, surgeon-to-patient phone calls may better optimize which patients with early-stage hormone receptor—positive breast cancer are best suited to continue on prolonged endocrine therapy and delay surgery from those who are at a higher risk, such as patients with an aggressive hematologic malignancy who require stem cell transplantation. Further, enrollment in clinical trials will likely be limited to those who are most likely to benefit from treatment.

The CDC is also implementing its pandemic preparedness and response plans and working on multiple fronts to issue specific guidance to better prepare communities to respond to local spread of COVID-19. Although not specific to oncology care providers, the CDC’s site includes current interim guidances on evaluating and testing people for COVID-19 and on the clinical care of people with COVID-19, as well as resources for healthcare professionals caring for patients with COVID-19. There is also information about how healthcare professionals can reduce their own risk of exposure to COVID-19, and includes guidance and resources on infection control, isolation protocols, and personal protective equipment.

“One best practice is to screen all patients who enter the clinic and triage those who are sick,” Neubauer added in his response. “Keeping staff safe and healthy must be a top priority so these professionals can continue to come to work and care for patients. The best way to minimize COVID-19 exposure is with proper personal protective equipment, which is needed by many healthcare professionals at this time. The challenges will be many, but oncology professionals are dedicated, willing and determined to keep their doors open to provide life-saving treatment during this global health crisis.”

American Society of Clinical Oncology (ASCO)

ASCO’s coronavirus resources website aims to provide oncology professionals with information and links about COVID-19. In general, ASCO is encouraging anyone caring for patients with cancer to follow the existing CDC guidance where possible. After collating questions from oncology professionals, ASCO also developed a frequently asked questions (FAQs) section and issued responses based on PubMed search of the relevant literature as well as available information from the CDC, WHO, and others.

There is no specific guidance with respect to COVID-19 testing in patients with cancer and ASCO recommends that clinicians follow local and state public health directives and guidance on who should be tested and how the tests should be conducted should be followed. Scheduling routine follow-up visits for patients not on active anticancer treatment should be considered for postponement or conducted via telemedicine. To avoid unnecessary visits to the clinic, at-home routine lab sample collection should be considered.

ASCO says clinicians and patients will need to make individual determinations based on the potential harms of delaying needed cancer-related surgery. Additionally, ASCO recommends that patients scheduled for immunosuppressive therapy should be screened for COVID-19 prior to therapy. In addition, delaying an allogeneic stem cell transplant may be reasonable, particularly if the patient’s malignancy is controlled with conventional treatment. Until further data are available, clinicians are encouraged to follow the recommendations provided by the American Society of Transplantation and Cellular Therapy (ASTCT); 

https://www.astct.org/connect/astct-response-to-covid-19

) and the European Society for Blood and Marrow Transplantation (EBMT) with respect to stem cell transplantation (

https://www.ebmt.org/ebmt/news/coronavirus-disease-covid-19-updated-ebmtrecommendations-8th-march-2020

Additionally, there is no specific evidence or published guidance to support delaying or interrupting adjuvant chemotherapy. Clinical decisions should be individualized considering factors such as the risk of cancer recurrence if adjuvant chemotherapy is delayed, modified or interrupted, the number of cycles of adjuvant chemotherapy already completed and the patient’s tolerance of treatment.

If a patient is diagnosed with COVID-19 on active anticancer treatment, ASCO states to follow the standard clinical management plans for delay or modification of cancer treatments in patients with active infection.

For the latest information and guidance documents, visit 

https://www.asco.org/asco-coronavirus-information

COA is providing practice resources and protocols on its COVID-19 resource page. Oncology providers can sign up for a free listserv that allows practice professionals to ask questions, network with each other, and share resources.

Available resources include access to data as they become available. One such study from China evaluated the efficacy of tocilizumab as a treatment in severe patients diagnosed with COVID-19.

 In this study, patients diagnosed as severe or critical COVID-19 were given tocilizumab in addition to routine therapy. Body temperature of all patients returned to normal on day 1 after receiving tocilizumab and remained stable then after. Fifteen of the 20 patients (75.0%) had lowered their oxygen intake and 1 patient required no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% patients (17/20) before treatment returned to normal in 52.6% patients (10/19) on day 5 after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% patients (16/19). No obvious adverse reactions were observed, and the authors stated that clinical symptoms of all patients improved with good prognosis.

Another available resource developed by the National Foundation for Infectious Diseases and the Alliance for Aging Research, aims to answer questions about why older people and people with health conditions are more at risk for COVID-19 infection as well provide guidance on best practices for this patient population.

 Compromised immune systems are more common in older populations, as well as in those with chronic medical conditions, making this population more susceptible to serious complications from the virus. Recommendations for this population include asking your physician or local pharmacy if ordering online is an available option, looking into online grocery orders, and guidance on what steps to take if symptoms arise.

https://communityoncology.org/coronavirus-covid-19-practice-resources-and-protocols/

NCCN Member Institutions are sharing insights and information to help providers respond to COVID-19. These include a factsheet for patients and visitor policy from Huntsman Cancer Institute. Included on the Huntsman site is a document to help oncology care professionals discuss COVID-19 with their patients.

 It advises physicians and patients to limit visitors, practice good hygiene, and watch for signs of infection. Patients are advised to contact their physician if they experience a fever higher than 100.3 degrees F, they feel short of breath, or they develop a cough, runny nose, or congestion.

Self-screen signs from the University of California San Francisco are also available for download. Provided in English, Spanish, Russian, Simplified and Traditional Chinese, the signs advise anyone with a cough, fever, or difficulty breathing to place a mask on immediately and instruct viewers to inform the front desk of any travel outside of the United States in the past few weeks. The NCCN plans to update the site as more resources become available.

https://www.nccn.org/covid-19/default.aspx

: The AMA has several resources for physicians: a physician’s guide to COVID-19 and FAQs, past publications on vaccine development, infection control, and public health preparedness. Also featured are research papers on the epidemiology of COVID-19, clinical management, health preparedness, and information for patients. For more information, visit 

https://www.ama-assn.org/delivering-care/public-health/covid-19-2019-novel-coronavirus-resource-center-physicians

: The FDA’s resource page includes updates on the latest research, including potential COVID-19 diagnostics, FAQs, and the agency’s role in developing medical countermeasures. The FDA issued on March 20 a new guidance for conducting clinical trials during the COVID-19 pandemic.

 The agency recognizes that challenges may arise, for example, from quarantines, site closures, travel limitations, interruptions to the supply chain for the investigational product. The FDA is aware that protocol modifications may be required, and that there may be unavoidable protocol deviations due to COVID-19. For more information, visit 

https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/coronavirus-disease-2019-covid-19

: WHO is gathering the latest scientific findings and knowledge on COVID-19 and compiling it in a database, including an update on research, an international clinical trials registry, and a database of publications on COVID-19. For more information, visit 

https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov

Ueda M, Martins R, Hendrie Paul, et al. Managing cancer care during the COVID-19 pandemic: agility and collaboration toward a common goal [published online March 17, 2020]. 

. doi: 10.6004/jnccn.2020.7560.           

Physicians treating patients with cancer may want to consider postponing surgeries or altering therapy plans because of the threat that the coronavirus poses to this population.

Denise Myshko

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