publication date: Apr. 10, 2020
ASCO publishes guidance on allocation of limited resources
The American Society of Clinical Oncology April 9 published a set of recommendations to support the oncology community as health care institutions across the United States face potentially difficult decisions around the allocation of scarce health care resources during the COVID-19 pandemic.
In some geographic areas, the crisis is expected to demand more resources—including ventilators, critical and intensive care beds, and medications—than the U.S. or local health care systems can supply, and institutions will need to develop allocation decision policies as they provide care for a growing number of patients.
ASCO’s recommendations assert:
Institutions should develop a fair and consistent prioritization and allocation policy before allocation becomes necessary. Decisions should be made at an institution-level, rather than at the bedside, so that oncologists can continue to maintain their duty to their patient.
Allocation of resources in a pandemic should be based on maximizing health benefits. Rationing for lifesaving critical care resources should not use assessments about the perceived quality of a patient’s life or perceptions about a patient’s social worth.
Oncologists should work with their institutions on how best to utilize scarce resources for care and support of cancer patients.
Oncologists should communicate allocation plans and decisions to their patients with compassion and honesty, and health care institutions should offer support to oncologists in these communications.
Oncologists should engage in advance care planning discussions with their patients and carefully document patient preferences for goals of care, particularly end of life care.
ASCO released the recommendations both in response to member reports that cancer care is being affected by the pandemic and to anticipate and inform the growing number of conversations happening at many institutions about resource allocation. The most critical aim is to ensure that the perspectives of patients with cancer and oncologists are included in all such discussions and decisions. The recommendations were developed by the ASCO Ethics Committee, approved by the board of directors, and accepted after peer review for future publication in the Journal of Clinical Oncology.
“As health care institutions make difficult decisions about where and how to deploy their resources during the COVID-19 crisis, they must ensure that allocation approaches don’t unconditionally deny patients with cancer access to resources,” ASCO President Howard A. “Skip” Burris III, said in a statement. “Every person with cancer has inherent worth and dignity. A cancer diagnosis alone should not keep a patient from a fair chance to access potentially life-saving resources, even in a public health crisis.”
ASCO’s recommendations aim to encourage the development of fair and equitable policies at the health system level for allocation of resources, especially critical care sources, and are not intended to guide individual treatment decisions. The recommendations also strive to promote the involvement of oncologists in the development and implementation of these policies to ensure that the needs of patients with cancer and their care teams are factored into the development of institutional policies. Individual oncologists will find guidance in ASCO’s recommendations about their critical role in caring for and advocating for patients who could potentially benefit from resources that are in scarcity during this time of crisis.
“Oncologists have great skill and expertise in treating the individual patient in front of them, but in a public health emergency like this one, we need to expand our view to also protect the health of the larger patient population,” Jonathan M. Marron, chair-elect of ASCO’s Ethics Committee and lead author of the recommendations, said in a statement. “Oncologists have an important role to play to promote resource allocation plans that fairly, objectively, and consistently consider patients with cancer, and to work with their institutions to communicate those decisions clearly to patients, families, and surrogates.”
COVID-19 cancer registry aims to track impact on patients during pandemic, inform care
The American Society of Clinical Oncology has launched an ASCO survey on COVID-19 in Oncology Registry to help the entire cancer community learn about the pattern of symptoms and severity of COVID-19 among patients with cancer, as well as how COVID-19 infections impact the delivery of cancer care and patient outcomes.
The registry will collect both baseline and follow up data throughout the COVID-19 pandemic and into 2021.
“As this unprecedented public health crisis continues, we’re seeing that certain populations – including individuals with cancer – are more likely to be vulnerable to the worst outcomes from COVID-19,” ASCO President Howard “Skip” Burris III, said in a statement. “The cancer care community needs data on how the virus is impacting our patients, their cancer treatment, and outcomes to inform current cancer care and decision-making for future disease outbreaks. We encourage all oncology practices to participate so that we can learn from every patient, in every practice, in every state across the country.”
Once sufficient patient data have been received and analyzed, ASCO will deliver periodic reports to the cancer community and the broader public on key learnings, such as characteristics of patients with cancer most impacted by COVID-19, estimates of disease severity, treatment modifications or delays, implementation of telemedicine in the cancer treatment setting, and clinical outcomes among patients related to both COVID-19 and cancer. ASCO also plans to develop peer-reviewed manuscripts based on the data provided.
The ASCO Registry is designed to capture not just point-in-time data on patients with cancer, but longitudinal data on how the virus impacts care and outcomes during the COVID-19 pandemic and into 2021.
“By looking at longitudinal data on patients, we’ll be able to learn more about the longer-term of effects of COVID-19 and its impact on cancer care,” Burris said. “We hope to learn if the virus resulted in specific complications for patients, delayed patients’ ability to get a specific type of treatment, or if certain approaches resulted in better outcomes for patients.”
Participating practices will be asked to complete a baseline data capture form on each patient with cancer who has a confirmed diagnosis of COVID-19, and subsequent follow-up information on status, treatment, and outcomes.
Limited patient identifying data, including zip code, date of birth, gender, race, ethnicity, type of cancer, and comorbidities, will be collected in a secure way to make longitudinal analysis possible. Data from practices participating in the registry will be collected and securely stored on the CancerLinQ platform. Additionally, CancerLinQ will be capturing data directly from CancerLinQ-participating practices on COVID-19 infection in their patients with cancer to allow for future analyses.
The web-based registry is open to all U.S. oncology practices, including physician-owned, academic, hospital/health system-owned practices, and hospitals, and will collect data from patients with all types of cancer who are undergoing all types of cancer treatment.
All participating practices will receive nominal financial support to cover research data-entry costs. The funding is supported by Conquer Cancer, The ASCO Foundation.
Six practices have already expressed interest in participating in the ASCO Registry: Oncology Hematology Care, Inc. (Cincinnati, Ohio), Winship Cancer Institute of Emory University (Atlanta, Georgia), Virginia Cancer Specialists (Alexandria, Virginia), Levine Cancer Institute, Atrium Health (Charlotte, North Carolina), Mayo Clinic (Rochester, Minnesota; Scottsdale and Phoenix, Arizona; and Jacksonville, Florida), and Hartford Healthcare Cancer Institute (Hartford, Connecticut).
AACR to split virtual annual meeting into two parts
The American Association for Cancer Research has split its virtual annual meeting into two sessions, which will be held in April and in June.
“AACR has been closely monitoring the rapid escalation of the COVID-19 pandemic,” the AACR board said in a statement. “The health and safety of all annual meeting attendees and the patients and communities they serve are the AACR’s highest priorities. Therefore, the AACR board of directors has made the decision not to move forward with an in-person annual meeting in August, and instead to present segments of the meeting program in two AACR virtual annual meetings.”
Here is how the sessions will be split:
April 27-28, 2020: AACR Virtual Annual Meeting I. This virtual meeting will feature a selection of high-impact proffered paper presentations. The program will include a number of clinical trial plenary sessions featuring more than 30 oral presentations along with perspectives on the science behind the clinical trials by expert discussants; clinical trial poster sessions; several minisymposia that showcase basic and translational science; and three New Drugs on the Horizon symposia that include first disclosures of innovative small molecules and biologics that have recently entered phase I clinical trials. Access to AACR Virtual Annual Meeting I will be made freely available. The abstracts of these proffered paper presentations will be posted online at 12:01 a.m. EDT (U.S.) on Monday, April 27.
June 22-24, 2020: AACR Virtual Annual Meeting II. The second virtual annual meeting will present thousands of proffered papers in minisymposia and in an e-poster platform. This meeting will also include an exciting opening plenary session with presentations on the latest developments in tumor biology and genetics (including the microenvironment), early detection, precision oncology, and cancer immunotherapies; the Presidential Address; the Presidential Select Symposium on precision pediatric cancer medicine; scientific merit and distinguished public service award lectures from individuals who have made extraordinary contributions to the cancer field; and a comprehensive educational program featuring about 70 educational sessions and methods workshops. Further details on the program, information regarding registration for AACR virtual annual meeting II, and guidance in obtaining any refunds of registration fees for the in-person April 2020 annual meeting will be communicated as soon as possible. Abstracts of the proffered paper presentations presented in this virtual meeting will be posted online at 12:01 a.m. EDT (U.S.) on Friday, May 15.
FDA approves first generic of commonly used albuterol inhaler to treat and prevent bronchospasm
FDA has approved the first generic of Proventil HFA (albuterol sulfate) Metered Dose Inhaler, 90 mcg/Inhalation, for the treatment or prevention of bronchospasm in patients four years of age and older who have reversible obstructive airway disease, as well as the prevention of exercise-induced bronchospasm in this age group.
“The FDA recognizes the increased demand for albuterol products during the novel coronavirus pandemic,” FDA Commissioner Stephen M. Hahn, said in a statement. “We remain deeply committed to facilitating access to medical products to help address critical needs of the American public.”
According to the National Heart, Lung, and Blood Institute, bronchospasms occur when the muscles surrounding the airways swell and tighten, causing them to squeeze the airways and make them smaller. Exercise and other physical activity can bring on symptoms in most people who have asthma and may occur either during or right after being active. Asthma causes recurring periods of wheezing (a whistling sound when breathing), chest tightness, shortness of breath and coughing. The coughing often worsens at night or early in the morning.
In March 2020, FDA issued a revised draft product-specific guidance for proposed generic albuterol sulfate metered dose inhalers, including drug products referencing Proventil HFA. Among other things, the draft guidance provides bioequivalence recommendations.
FDA requires applicants to submit appropriate data and information to demonstrate that complex generic drug-device combination products meet the agency’s rigorous approval standards. These standards ensure quality generic drug products are as safe and effective as their brand name counterparts.
The FDA granted approval of this generic albuterol sulfate inhalation aerosol to Cipla Limited.
COA establishes practice referral service for patients seeking cancer treatment during COVID-19 pandemic
Hospitals have scaled back or closed cancer and blood disease services to make space for patients with COVID-19.
Recognizing that cancer care must continue, the Community Oncology Alliance has launched a referral service for patients seeking care in their communities.
Through the COA Patient-Practice Connector website, patients seeking care can fill out a brief contact form without sharing any personal health information. The COA team will then use that information to try to identify a practice that is still serving patients in their community within 24 hours.
The COA Patient-Practice Connector minimizes the amount of exposure that cancer patients may face when trying to find treatment. The website makes it easier to maintain social distance and find the provider that is the best fit for the patient.
No patient data will be stored or shared, and users can choose their provider. All data submitted to COA will be deleted immediately once a request is closed.
COA opposes home infusion for cancer, citing safety concerns
The Community Oncology Alliance board of directors released a position statement opposing the home infusion of chemotherapy, cancer immunotherapy, and cancer treatment supportive drugs because of serious patient safety concerns.
The home infusion of cancer treatments by a provider who may not be a trained oncology nurse and may not recognize or be prepared to treat any of the serious adverse reactions that frequently occur is of significant concern, the statement said.
Many of the side effects caused by cancer treatment can have a rapid, unpredictable onset that places patients in incredible jeopardy and can even be life-threatening. Home infusion negates the benefits of the expertise and team approach to cancer care, which are the hallmarks of community oncology, within facilities specifically designed for safe and effective cancer drug infusions.
The COVID-19 pandemic has forced all health care providers and care settings to dramatically adjust operations. Independent, community oncology practices have quickly adapted and are taking extreme measures to keep their facilities and providers COVID-19 free so that their patients in active treatment can be assured of a safe environment. The recent, major expansion of telehealth services and relaxation of regulations has provided oncologists with a powerful tool to do this by monitoring patients and ensuring that only those that are in urgent need of treatment come into the practice.
The COA home infusion position statement notes that there are other medical specialties and diseases where the infusion of Medicare Part B drugs at home may be reasonable during the COVID-19 pandemic. As such, the position is currently limited to opposition for the home infusion of cancer treatments.
GO2 Foundation for Lung Cancer: COVID-19 patients with pre-existing conditions should receive same treatment as those without
GO2 Foundation for Lung Cancer is working with value-based coalitions to address the concerns of discrimination in access to treatment to make sure that our lung cancer community is not disadvantaged during the COVID-19 crisis.
“The Americans with Disabilities Act: Section 504 of the Rehabilitation Act and Section 1557 of the Affordable Care Act provides protection from healthcare discrimination.
Because of concerns about pre-existing conditions and disability discrimination in access to treatment has been a major concern during the COVID-19 crisis, the Department of Health and Human Services’ Office of Civil Rights issued guidance to covered healthcare entities (anyone that accepts federal funding) on protecting individual civil rights and privacy during the COVID-19 emergency.
The guidance states that “persons with disabilities should not be denied medical care on the basis of stereotypes, assessments of quality of life, or judgments about a person’s relative worth based on the presence or absence of disabilities. Decisions by covered entities concerning whether an individual is a candidate for treatment should be based on an individualized assessment of the patient based on the best available objective medical evidence.”
While this guidance is not a new law it is a step in addressing civil rights concerns as potential rationing of health services comes closer to reality.
The guidance would be extended to persons with pre-existing or severe chronic health conditions.
The “Know Your Rights” fact sheet explains protections and provides direction on filing a complaint of discrimination.
“We are adding the voice of the lung cancer community with the disabilities community in supporting these guiding principles,” the foundation said in a statement. “These principles reinforce our civil rights laws that protect equal dignity for every human life and that healthcare providers should not discriminate against those with disabilities nor put at the end of the line for health services during emergencies.”
Algorithm aims to protect surgical team members against infection with COVID-19 virus
Researchers from Stanford University’s Department of Surgery have created an algorithm that aims to protect operating room team members who perform urgent and emergency operations from COVID-19, and rationally conserve the personal protective equipment they wear.
This best practice guideline is published in the Journal of the American College of Surgeons ahead of print. Stanford Health Care serves Santa Clara and San Mateo Counties, which saw their first cases of COVID-19 infection in early March.
The Stanford algorithm is based on the urgency of the procedure, potential for aerosolization and release of virus droplets at the surgical site, and evidence that a patient has been infected. The algorithm aligns with the goals of the ACS statement on PPE Shortages during the COVID-19 Pandemic, released April 1.
“We developed institutional guidelines based on how soon the surgical cases needed to be performed, the patient’s condition, the risk that a surgeon would access an area of body where the amount of virus could be high, and the risk that a patient could be infected with COVID-19,” Joseph Forrester, an assistant professor in general surgery and lead author of the algorithm article, said in a statement.
Forrester was a field agent in Liberia during the 2014 Ebola outbreak where he conducted several investigations of the Ebola burden and preparedness as an Epidemic Intelligence Service officer with CDC.
At Stanford, a PPE task force of hospital and medical school leaders from interventional suites, including the operating room, interventional radiology, and endoscopy, as well as quality improvement and infectious disease experts, convened on March 19 to create institutional guidelines that could be implemented within 72 hours. At that time, Stanford Health Care had approximately 10 patients infected with COVID-19. Guidelines incorporated current data about COVID-19 transmission in hospital and non-hospital settings and operating room risk during outbreaks of SARS and Ebola.
Patients were triaged by severity of illness into urgent and emergency procedures. Urgent cases were stratified into high- and low-risk procedures depending on the expected viral burden at the surgical site. Procedures categorized as aerosol-generating were classified as high-risk. These procedures include those that involve the aerodigestive tract, endoscopy, and open or laparoscopic surgery on the bowel with gross contamination.
The Stanford guideline assumes, above all, that any patient could be infected with COVID-19 unless proven otherwise by a negative RT-PCR test. When operating on COVID-19-positive patients or performing an AGP, the guideline requires operating room team members to be fitted with an N-95 respirator mask and wear a gown, gloves, and eye protection. Only when an RT-PCR test is negative for COVID-19 may surgical team members wear standard surgical clothing.
A surgeon may consider delaying an urgent or emergency procedure on a patient who exhibits viral symptoms (fever, cough, sore throat). If delay compromises the well-being of the patient, the surgeon orders in-house RT-PCR COVID-19 testing with a 24-hour turnaround. If the patient’s status does not allow for a 24-hour wait, the case is considered to be an emergency and the patient is presumed to be COVID-19-positive.
Special considerations are made for the use of PPE during and after bag mask ventilation and endotracheal intubation, which both pose a high risk for viral transmission. All health care providers who are not directly involved with intubation are asked to leave the operating room beforehand. Anesthesiologists should be fitted with N-95 face masks and droplet-protective PPE because they are positioned at the head of the bed throughout the procedure. Cleaning staff should take droplet precautions when cleaning any operating room.
At the time the guideline was created at Stanford Health there was a nationwide shortage of N-95 face masks. To conserve the institution’s supply, the algorithm requires a face shield to be placed over the mask.
Karyopharm to evaluate low-dose Xpovio as potential COVID-19 treatment
A global randomized clinical trial for low dose oral Xpovio (selinexor) in hospitalized patients with severe COVID-19 aims to evaluate the drug as a potential treatment option.
Karyopharm Therapeutics Inc. sponsors the drug.
FDA has approved Xpovio as a treatment for patients with relapsed or refractory multiple myeloma. Selinexor is an oral, selective inhibitor of nuclear export compound that blocks the cellular protein XPO1.
In addition to its roles in cancer, XPO1 also facilitates the transport of several viral proteins from the nucleus of the host cell to the cytoplasm, and it amplifies the activities of pro-inflammatory transcription factors.
SINE compounds have been shown to disrupt the replication of multiple viruses in vitro and in vivo. They have also been shown to mediate anti-inflammatory and anti-viral effects, including respiratory infections, in several animal models. In particular, SINE compounds have recently been identified as having the potential to interfere with key host protein interactions with SARS-CoV-2, the virus that causes COVID-19.2
Selinexor is the only XPO1 inhibitor approved for commercial use by the FDA and has been extensively tested in clinical trials across numerous cancer indications worldwide since 2012. The proposed clinical trial to treat hospitalized patients with COVID-19 would be the first study of an XPO1 inhibitor in patients with severe viral infections.
“While Karyopharm’s clinical development strategy until now has been focused on patients with various types of cancer, there is increasing evidence that XPO1 inhibition could play an important role in the treatment of patients with viral infections including SARS-CoV-2,” Sharon Shacham, president and chief scientific officer of Karyopharm, said in a statement.
“As the medical community is urgently seeking innovative ways to address the COVID-19 pandemic, based on recent scientific data, we have decided to evaluate the potential for selinexor in the treatment of patients with COVID-19. We look forward to working with clinical investigators and regulators across the globe as expeditiously as possible to determine the next steps for this new initiative.
“Additionally, we continue to move our oncology programs forward including the expected submission of our BOSTON supplemental New Drug Application in the second quarter of this year,” Shacham said.
“I am highly encouraged by the scientific rationale of studying selinexor, which targets both virus and immune-mediated injury, for treatment of patients with severe COVID-19,” Thomas J. Walsh, professor of medicine, pediatrics, and microbiology & immunology, Weill Cornell Medicine, Cornell University, said in a statement.
SINE XPO1 inhibitors have demonstrated activity against over 20 different viruses, including the RNA viruses, influenza, respiratory syncytial virus and other common causes of respiratory infection. XPO1 inhibition has been identified in several assays as having potential activity against SARS-CoV-2, although specific animal models have not been available to date. One of the most important aspects of COVID-19 is the marked pulmonary inflammation with high levels of cytokines such as IL6, IL1, IFNg and others. Along these lines, selinexor and other SINE compounds have demonstrated potent anti-inflammatory activity through the inhibition of Nuclear Factor kB (NF-kB), leading to reductions in all of these cytokines in a variety of models, and this may be particularly beneficial to hospitalized patients with COVID-19.
GSK and Vir Biotechnology collaborate to find COVID-19 solutions
GlaxoSmithKline plc. and Vir Biotechnology Inc. are collaborating on research solutions for coronaviruses, including SARS-CoV-2.
The binding agreement will use Vir’s proprietary monoclonal antibody platform technology to accelerate existing and identify new anti-viral antibodies that could be used as therapeutic or preventative options to help address the current COVID-19 pandemic and future outbreaks. The companies will leverage GSK’s expertise in functional genomics and combine their capabilities in CRISPR screening and artificial intelligence to identify anti-coronavirus compounds that target cellular host genes. They will also apply their combined expertise to research SARS-CoV-2 and other coronavirus vaccines.
“Vir’s unique antibody platform has precedented success in identifying and developing antibodies as treatments for multiple pathogens, and it is highly complementary with our R&D approach to focus on the science of immunology,” Hal Barron, chief scientific officer and president of Research and Development at GSK, said in a statement.
The initial focus of the collaboration will be to accelerate the development of specific antibody candidates identified by the Vir platform, VIR-7831 and VIR-7832, that have demonstrated high affinity for the SARS-CoV-2 spike protein and are highly potent in neutralising SARS-CoV-2 in live virus-cellular assays. Subject to regulatory review, the companies plan to proceed directly into a phase II clinical trial within the next three to five months.
The collaboration will also utilise Vir’s CRISPR screening and machine learning approach to identify cellular targets whose inhibition can prevent viral infection. Vir has identified multiple potential targets against flu and other respiratory pathogens, as well as hepatitis B virus, and will now focus on SARS-CoV-2.
Additionally, the companies have also agreed to conduct research into SARS-CoV-2 and other coronavirus vaccines by coupling GSK’s vaccines technologies and expertise with Vir’s ability to identify neutralising epitopes that are present across entire viral families. These efforts will be additive to other initiatives GSK is advancing to develop a potential vaccine for COVID-19.
“It is becoming increasingly clear that multiple therapeutic approaches, used in combination or in sequence, will be necessary to stop this coronavirus pandemic. It is likely that the current coronavirus outbreak will not be the last,” George Scangos, CEO of Vir Biotechnology, said in a statement.
To gain access to Vir’s technology, GSK will make an equity investment in Vir of $250 million, priced at $37.73, a 10% premium to the closing share price on March 27.
OncoSec collaborates with Providence Cancer Institute to conduct phase I study of COVID-19 vaccine
Providence Cancer Institute, a part of Providence St. Joseph Health, has launched a phase I study of OncoSec’s novel DNA‑encodable, investigational vaccine, CORVax12, designed to act as a prophylactic vaccine to prevent COVID-19.
CORVax12 consists of OncoSec’s existing product candidate, Tavo (interleukin-12 or “IL-12” plasmid), in combination with an immunogenic component of the SARS-CoV-2 virus recently developed by researchers at NIH’s National Institute of Allergy and Infectious Diseases and licensed to OncoSec on a non-exclusive basis.
OncoSec’s CORVax12 vaccine approach combines the co-administration of Tavo (plasmid IL-12) with a DNA-encodable version of the SARS-CoV-2 spike or “S” glycoprotein to enhance immunogenicity of the component developed by scientists at the NIAID Vaccine Research Center. CORVax12 is designed to drive a coordinated vaccine response, capable of drawing upon the innate, adaptive humoral, and adaptive cellular arms. We believe this multi-pronged innate, adaptive and cellular immune response is likely to be important in generating a robust anti-viral response.
“Previous vaccine efforts against coronaviruses, including the SARS coronavirus, have focused on the S glycoprotein, which facilitates interaction with the host cell through binding to the ACE2 receptor,” principal investigator on the study Rom Leidner, co-medical director, of the Head and Neck Cancer Program at Providence Cancer Institute, and assistant member of the Earle A. Chiles Research Institute, said in a statement.
Providence investigators will evaluate the vaccination of healthy adult volunteers utilizing OncoSec’s next-generation, investigational APOLLO generator technology for the first time clinically if FDA clears the APOLLO to enter the clinic. The trial will also include extensive immune monitoring.
OncoSec will supply CORVax12 and its investigational APOLLO electroporation device to Providence as part of this effort and does not anticipate any additional capital commitment at this time. Additionally, OncoSec will contribute manufacturing, preclinical, and prior clinical information and data for TAVO, along with manufacturing data for its APOLLO technology, to support FDA’s allowance of the Providence IND. Providence will hold the IND, if cleared by FDA, and perform the preclinical and clinical development work.
FAQs and Guidances
American Society of Clinical Oncology FAQ: Emerging issues and challenges in caring for patients with cancer during the coronavirus pandemic
American Association for Cancer Research FAQ: Information on virtual annual meetings
American Cancer Society FAQ: Common questions about the new coronavirus outbreak
Society for Immunotherapy of Cancer Resources: Patient management and basic and translational research
Community Oncology Alliance resources: Coronavirus (COVID-19) practice resources and protocols
Leukemia & Lymphoma Society FAQ: Resources and what you should know about the coronavirus
American Society for Radiation Oncology FAQ: COVID-19 recommendations and information
American College of Surgeons resources: For the surgical community
Society for Immunotherapy of Cancer resources: Implications for patients, translational research
GO2 Foundation for Lung Cancer resources
American Society for Transplantation and Cellular Therapy resources
European Blood and Marrow Transplantation Society recommendations
World Marrow Donor Association resources
National Institute for Health Care Management Foundation resources