publication date: May. 1, 2020
AACR data from China and Europe amount to “two different messages” for cancer patients with COVID-19
By Alexandria Carolan
This story is part of The Cancer Letter’s ongoing coverage of COVID-19’s impact on oncology. A full list of our coverage, as well as the latest meeting cancellations, is available here.
Are COVID-19 patients with cancer at a greater risk of dying than non-cancer patients? Depends on whom you ask.
Researchers from China, Italy, France, Spain, and the United States presented data at the first-ever virtual annual meeting of the American Association for Cancer Research April 28 that demonstrated very different answers to this question.
“My general view—and I tried to bring it up in the discussion—was that we have two different messages: the one from the two presenters from Wuhan saying that patients with cancer do worse with COVID-19 infections,” Antoni Ribas, president-elect of AACR, said to The Cancer Letter. “That contrasts with the data that were provided from Italy, from France, and from Spain—where a cancer diagnosis was not an adverse prognostic factor for having a bad outcome with the COVID-19 infection.”
Ribas is a professor of medicine, professor of surgery, and professor of molecular and medical pharmacology at the University of California Los Angeles, director of the Tumor Immunology Program at the Jonsson Comprehensive Cancer Center, and chair of the Melanoma Committee at SWOG.
The data presented at an AACR session, titled “COVID-19 and Cancer,” were based on observational cohort studies in cancer patients with COVID-19. Several studies broke down fatality rate by cancer type.
Data from Italy and China earlier in the course of the pandemic suggest that patients with cancer, as with patients with comorbid conditions, are at higher risk for developing severe adverse events and dying after testing positive for SARS-CoV-2 (The Cancer Letter, March 20, April 3, 2020).
Results from Wuhan, published in Cancer Discovery, demonstrated that patients with cancer, specifically those who finished cancer treatment, were more at risk than those who had not gone through cancer treatment.
“This is consistent with what my concerns have been,” Leonard Lichtenfeld, deputy chief medical officer at American Cancer Society, said to The Cancer Letter. “The numbers are small, but they confirm the concerns and fears of many of us, that COVID-19 is worse for cancer patients. “Patients who get chemotherapy, or patients who have recovered from lymphoma, still could have some impact on their immune system. And the Wuhan data support that. On the other hand, other data does not support that. So we have a lot to learn.”
Researchers from Gustave Roussy reported that the rate of infection does not seem higher in cancer patients than in the global population, justifying “an optimal management of the cancer patients’ underlying tumor.”
“The bottom line is when we talk about patients with cancer, the ones who are in acute treatment, we all know have to be protected. But we also have a vulnerable population of those who have recovered, who are survivors, who tend to be older, who had cancer,” Lichtenfeld said. “And that is a group I’m particularly concerned about as we do these opening orders, because they need to understand, their families need to understand.”
Types of cancer most common in Europe could be different from those found in China, observers say.
“Different information from China and from Europe may be based on referral patterns, type of disease, and comorbid conditions,” Ribas said. “In the European series, the patients who had a prior cancer but are not being actively treated for it, did not do worse than the patients who were actively treated unless they had a very recent chemotherapy or a hematologic cancer.”
“It was patients who had comorbid conditions—in particular in the lungs, patients who have chronic lung inflammatory disease are also more likely to have lung cancer, both linked to cigarette smoking,” Ribas said.
Conclusions from the abstracts presented during the COVID-19 and Cancer session follow:
The experience of treating patients with cancer during the COVID-19 pandemic in China, presented by Li Zhang of Tongji Hospital in Wuhan.
“Cancer patients showed aggressive presentation and poor outcomes with the COVID-19 infection. It is recommended that vigorous screening for COVID-19 infection should be performed for cancer patients with anti-tumor. From our limited data, there is no evidence to suggest difference in cancer patients on ICI treatment.”
Patients with cancer appear more vulnerable to SARS-CoV-2: A multi-center study during the COVID-19 outbreak, presented by Hongbing Cai, of Zhongnan Hospital of Wuhan University, Wuhan.
“Our results showed COVID-19 patients with cancer had higher risks in all severe outcomes. Patients with hematological cancer, lung cancer, or with metastatic cancer (stage IV) had the highest frequency of severe events. Non-metastatic cancer patients experienced similar frequencies of severe conditions to those observed in patients without cancer. Patients who received surgery had higher risks of having severe events, while patients with only radiotherapy did not demonstrate significant differences in severe events when compared to patients without cancer. These findings indicate that cancer patients appear more vulnerable to SARS-COV-2 outbreak. Since this is the first large cohort study on this topic, our report will provide the much-needed information that will benefit global cancer patients. As such, we believe it is extremely important that our study be disseminated widely to alert clinicians and patients.”
TERAVOLT (Thoracic cancERs international coVid 19 cOLlaboraTion): First results of a global collaboration to address the impact of COVID-19 in patients with thoracic malignancies, presented by Marina Chiara Garassino of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
“Data suggest that due to their cancer diagnosis patients with thoracic malignancies are less likely to be admitted to the intensive care unit and are at increased risk of prolonged hospitalization and mortality from COVID-19 infection. With improved cancer therapeutic options and prognosis, physicians need to balance the individual cancer specific mortality and risk of death when treating patients with COVID-19. TERAVOLT will continue to collect data and to provide data in order to identify characteristics associated to a severe COVID-19 able to help societies to create guidelines tailored on individual risk.”
Experience in using oncology drugs in patients with COVID-19, presented by Paolo A. Ascierto, of Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples.
“The hyperactivation of immune system due to the immunotherapy strategies can develop some conditions which need of immuno-suppressive drugs to reduce the harmful immune reaction. Since the acute respiratory stress syndrome COVID-19 related seems to occur from an excess of cytokine production, we focused our attention on the cytokines storm which probably lead to ARDS by COVID19 and how to prevent or treat it. We know very well the Cytokine Release Syndrome (CRS), one of the most prominent and well described toxicity from chimeric antigen receptor T cell therapy (CAR-T), as well as from some bispecific antibodies. In particular, we know the key role played by IL-6 in the pathogenesis of these kind of hyperinflammation syndromes. Considering elevated serum concentration of IL-6 and CPR in patients admitted in ICUs department, we started to use monoclonal antibodies against IL6, above all tocilizumab. In Italy we started on 19th of March a phase II study (NCT04317092) which enrolled 330 patients in 24 hours, with the ability of tocilizumab to reduce the one-month mortality rate as main endpoint.”
Outcome of cancer patients infected with COVID-19, including toxicity of cancer treatments, presented by Fabrice Barlesi, of Gustave Roussy Cancer Campus, Villejuif, France.
“Globally, the rate of the SARSCoV-2 infection in our cancer patients’ population does not seem to be higher compared to the global population. We have not found evidence that COVID19 is more lethal or aggressive in cancer patients that underwent usual SARS-Cov-2 treatment. We believe that adequate testing and protective measures, along with the low rate of SARS-cov-2-treatment-related adverse events (5.5%), justify an optimal management of the cancer patients’ underlying tumor.”
Adapting oncologic practice to COVID19 outbreak: From outpatient triage to risk assessment for specific treatment in Madrid, presented by Carlos Gomez-Martin, of Octubre University Hospital, Madrid.
“Until data from randomized studies including cancer patients were available, their diagnosis and treatment must be carried out according to the standard of care at all times. Comorbidities and life expectancy conditioned the treatment by the underlying tumor must be taken into account when considering an aggressive treatment (ICU). Based on our data, lung involvement (primary or metastatic), neutropenia and acute respiratory distress syndrome are predictive factors of poor outcome (death) regardless of other conditions. COVID-19 treatment must be multidisciplinary and it should include specific antiviral therapy, supportive treatment, close monitoring of inflammatory parameters, and appropriate use of anticoagulants given the risk of thromboembolic complications in this disease.”
AACR record attendance: 61,000 registered
The first-of-its-kind virtual AACR meeting marks the beginning of the 2020 conference season, nearly all of which will take place online this year.
The 61,000 people in attendance was “unexpected,” said Antoni Ribas, president-elect of the association. The highest-attended AACR meeting in the past had about 20,000 in attendance, Ribas said.
“We imposed on ourselves to create something that hasn’t been done before, and make it freely available to everyone,” Ribas said. “We were excited to provide a scientific program with many sessions but we knew it would be a big challenge to organize it in such a short period of time.”
“We’re going to emerge out of this and it’s going to be the same principles that we’ve had so far where science and knowledge will allow us to move forward. It will be applied to the COVID-19 pandemic, and it will be applied to cancer research and cancer treatment,” Ribas said.
The AACR annual meeting represents the first opportunity for the global cancer research community to share data on COVID-19 and formulate strategies to treat the disease.
Pre-COVID-19, the observational cohort studies presented at the AACR session would have been considered “hypothesis generating,” Karen Reckamp, director of Medical Oncology, associate director of Clinical Research, and director of Medical Oncology at the Lung Institute at Cedars-Sinai Medical Center, said to The Cancer Letter.
“In the cancer world, there’s been very limited data that has helped us to understand how best to treat our patients with cancer,” Reckamp said. “Now, when you bring even a little bit of data into that vacuum, you want to fill up the void. I think we have to remember that, even at a place like AACR, generally when we’re at those meetings—even a randomized phase III trial can be debated by the scientists that are there to talk about the merits of what might be the gold standard.”
Data from countries hit hard with the novel coronavirus can be applied in pandemic hotspots in the United States—such as New York.
“It’s helpful now that we’re getting some data from other centers, and helpful that from other centers around the world, we understand some local issues,” Reckamp said. “I think some of the issues brought out by some of the European data, is that when you do have less resources, it really may be that cancer patients may do worse if they’re not able to get the resources that are available.
“Also thinking about the New York data, and the social and economic issues faced by patients and issues of diversity, that not everybody has the same access or the same ability to socially isolate—and they may be at more risk,” Reckamp said.
During the session, Louis Voigt, an intensivist who is the chair of the Ethics Committee at Memorial Sloan Kettering Cancer Center, reviewed the limited data from his institution.
Source: Presented by Louis Voigt at AACR virtual annual meeting I.
MSK tested more than 5,000 patients for COVID-19, Voigt said. Of these, 773 patients tested positive, and 327 of them were hospitalized at the cancer center as of April 22. Fifty four percent of the cohort were discharged from the hospital, and 14% died in the hospital, Voigt said. The average full stay was 10 days.
In the ICU, as of April 22, 78 patients were admitted, and 52 of them needed mechanical ventilation. Thirteen patients were extubated, four underwent tracheostomy, 22 had a do not resuscitate order, 15 died in the hospital, and 40% were still receiving care in the ICU. Three patients were discharged.
Voigt provided a summary of what has been published so far for several cohorts of patients in Seattle, the United Kingdom, New York City at Northwell, and in New York City at Memorial Sloan Kettering. The MSK data have not been validated, and should not be considered published or final, Voigt said.
Source: Presented by Louis Voigt at AACR virtual annual meeting I.
“There was approximately anywhere between 56 and 88% of mortality recorded or reported for patients who required mechanical ventilation. That number contrasts with the 27% recorded mortality for patients with cancer admitted at Memorial Sloan Kettering Cancer Center,” Voigt said. “So, we are still gathering data and analyzing them. I did not present any real demographic variables, cancer types, active cancer directed therapies, CPR, or hematologic complications of aggressive anticoagulation to be followed.”
The MSK data, in combination with data from the other countries, leave researchers with more questions, Voigt said.
How does prior-immunotherapy affect COVID-19 infections? What is the impact of calibrated or reduced-dose chemotherapy? And what about the socioeconomic status of patients and characteristics of race, ethnicity, or limited-English proficiency?
“The deleterious effects of cancer and COVID-19 appear obvious. In fact, we have a higher incidence of cancer and cancer-related mortality as well as a high incidence of COVID-19 and COVID-19-related mortality, for African Americans and Hispanics, compared to the white population,” Voigt said.
The pandemic has created the perfect condition for suboptimal care and treatment for underserved populations, Voigt said.
“The decisions being made by many health care professionals are sometimes driven by fear and emotions rather than evolving facts,” Voigt said. “That should be a calling to all of us caring for patients, particularly patients with cancer, because our obligations for a more robust safety net for this vulnerable groups of patients remain, and become, in fact, more needed—as defined by ASCO, by AACR, by ACS and by NCI.”
“We need to be careful, because the reality may be more complex and we need more time and more data,” Voigt said.
Breaking down the data by country
Two of the studies presented during the virtual session were from Wuhan. The first, The experience of treating patients with cancer during the COVID-19 pandemic in China, presented by Li Zhang of Tongji Medical College, defined the clinical characteristics of cancer patients with COVID-19 in three Wuhan hospitals from Jan. 13 through Feb. 26.
Specifically, the researchers followed 124 cancer patients with immune checkpoint inhibitors, and their families, for their infection rate and clinical outcome. The study included 28 COVID-19 patients who also had cancer, with a median age of 65 years. Seven (25%) of the patients had lung cancer, and eight (28.6%) had been infected while they were in the hospital.
Fifteen (53.6%) patients had severe events with a mortality rate of 28.6%. The last anti-tumor treatment within 14 days from the diagnoses of COVID-19 significantly increased risk of developing severe events (HR=4.079, 95%CI 1.086-15.322, P=0.037). The common chest CT findings were ground-glass opacity (21, 75.0%) and patchy consolidation (13, 46.3%). The patchy consolidation on CT had a higher risk for developing severe events (HR=5.438, 95%CI 1.498-19.748, P=0.010).
Only one patient (1/124, 0.8%), who had been on immune-checkpoint inhibitor treatment for his metastatic hepatocellular carcinoma and tested positive COVID-19 infection, had mild clinic presentation and a short hospital course.
Source: Presented by Li Zhang at AACR virtual annual meeting I
“Cancer patients with COVID-19 presented poor outcomes with higher occurrence of clinical severe events and mortality. The antitumor treatment within 14 days of COVID-19 diagnosis increased the risk of developing severe events,” Zhang said at the session. “Limited information did not suggest cancer patients treated with immune checkpoint inhibitors were more vulnerable to the COVID infection, or with worse outcomes compared to the others.”
The second study, Patients with cancer appear more vulnerable to SARS-COV-2: A multi-center study during the COVID-19 outbreak, presented by Hongbing Cai, of Zhongnan Hospital of Wuhan University in Wuhan, observed the effects of COVID-19 on cancer patients, and categorized these by cancer type.
The study included 105 cancer patients and 536 age-matched non-cancer patients with confirmed COVID-19. Results showed COVID-19 patients with cancer had higher risks in all severe outcomes. The most frequent cancer types were lung, 22 (20.95%) of 105 patients, gastrointestinal, 13 (12.38%) of 105 patients, breast 11 (10.48%) of 105 patients, thyroid cancer 11 (10.48%) of 105 patients, and hematological cancer, nine (8.57%) of 105 patients.
Three out of nine patients (33.33%) with hematologic malignancies died. Four out of 22 patients with lung cancer died, with a mortality rate of 8.18%.
Source: Presented by Hongbing Cai at AACR virtual annual meeting I
“It’s a very small sample size, and it’s heterogeneous,” Noah Merin, assistant professor of medicine in the Clinical Scholar Track Blood and Marrow Transplantation Program at Cedars-Sinai Medical Center, said to The Cancer Letter. “Leukemia includes myeloid leukemia as well as one lymphoid leukemia, and then lymphoma and multiple myeloma are both lymphoid malignancies.”
“Those of us who treat hematologic malignancies are really interested to know whether patients who have low neutrophils, so monocytes, patients who may have consequences of myeloid malignancies, or targeting of myeloid diseases, have a different outcome from patients who have lymphoid malignancies,” Merin said. “Because it is a different type of an immunocompromised state that they’re in. It determines whether they have lower T-cell or hemo-immunity, versus lower myeloid immunity.”
The study included a similarly high in-hospital infection rate to the first study, at 19.04% for cancer patients, and 1.49% for non-cancer patients. The study found that We found that patients with metastatic cancer had even higher risks of death (OR 5.58, 95% CI [1.71, 18.23]; p=0.01), ICU admission (OR 6.59, 95% CI [2.32, 18.72]; p<0.01), having severe conditions (OR 5.97, 95% CI [2.24, 15.91]; p<0.01), and use of invasive mechanical ventilation (OR 55.42, 95%CI [13.21, 232.47]; p<0.01). In contrast, patients with non-metastatic cancer did not demonstrate statistically significant differences compared with patients without cancer, all with p values > 0.05.
Additionally, patients who received surgery had higher risks of having severe events, while patients with only radiotherapy did not demonstrate significant differences in severe events when compared to patients without cancer.
“The data from Wuhan, for example, of hospital-acquired infections and patients with cancer were 10 times greater than they were for patients without cancer. In certain cancers, were particularly—COVID-19 was particularly lethal. But again, the numbers were small,” Lichtenfeld said.
Conflicting conclusions from France
Fabrice Barlesi of Gustave Roussy Cancer Center in Villejuif, France, found that the coronavirus didn’t pose a greater risk to cancer patients who underwent treatment for COVID-19.
He presented the findings from the abstract titled Outcome of cancer patients infected with COVID-19, including toxicity of cancer treatments. At peak infection, more than 13,000 patients were positive for COVID-19 in the Paris area, Barlesi said.
Gustave Roussy tested 1,302 patients for COVID-19, and 12% were found positive. The study included 137 cancer patients diagnosed with COVID-19. The primary endpoint of this analysis was the clinical deterioration, defined as the need for oxygen supplementation of 6 l/min or more, or death of any cause.
Source: Presented by Fabrice Barlesi at AACR virtual annual meeting I
Most COVID-19-positive cancer patients were female (58%), with a median age of 61 years, including 36 pts (26%) ≥ 70 years. Most frequent underlying cancers were solid tumors (115) including breast (23), gastrointestinal (18), head and neck (17), genitourinary (17), gynecologic (17) malignancies or hemopathies (22).
At time of diagnosis, 79 patients (58%) had metastatic/active cancer, and 56 pts (41%) were considered in remission/treated with curative intent. The diagnosis of SARS-CoV-2 infection was made by RT-PCR or thoracic CT scan alone in 93.4% and 6.6% of the cases, respectively.
Clinical deterioration occurred in 34 pts (24.8%) and was associated with hematological underlying disease, CRP at diagnosis of COVID19 >50 and the use of cytotoxic chemotherapy within less than three months. At data cut-off April 20, 95 (69.3%), 20 (14.6%), and 22 (16.1%) patients were discharged, had died, or were still hospitalized, respectively, according to the abstract.
All the deaths were considered related to SARS-CoV-2 infection.
TERAVOLT: COVID-19 patients with lung cancer
Given that patients with thoracic malignancies have been shown to be at particularly high-risk—for example, in the Wuhan data—researchers from Italy created a global registry called TERAVOLT (Thoracic cancERs international coVid 19 cOLlaboraTion) to provide guidance to oncologists managing thoracic malignancies in the time of COVID-19.
Thoracic cancer patients are thought to be at particular risk given the number of potential risk factors: older age, smoking habits, pre-existing cardio-pulmonary concomitant comorbidities, and intensive therapies administered to treat their illness, Marina Chiara Garassino, of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, said during the session.
Garassino presented TERAVOLT (Thoracic cancERs international coVid 19 cOLlaboraTion): First results of a global collaboration to address the impact of COVID-19 in patients with thoracic malignancies.
Source: Presented by Marina Garassino at AACR virtual annual meeting I
The TERAVOLT study includes 200 patients who have COVID-19 and thoracic cancers, from eight countries. The median age of patients is 68 years, and 29.5% are women. The most common histology was non-small cell lung cancer, in 75.5% of patients, and small cell lung cancer, in 14.5% of patients. The majority of these patients, 73.5%, had stage IV disease.
Systemic therapies were done in 147 out 200 (73.5%) patients and included 19%, 32.7% and 23.1% of patients on TKI alone, chemotherapy alone, and immunotherapy alone—13.6% of patients were on a chemotherapy-immunotherapy combination. 152 (76.0%) patients were hospitalized and 66 (33.3%) died. The majority were not offered intensive care therapy.
Univariate analyses revealed that the presence of COPD, was associated with increased risk of hospitalization, and more than one comorbidity with increased risk of hospitalization and death. Tumor type and cancer therapy did not impact survival.
The second study from Italy, Experience in using oncology drugs in patients with COVID-19, presented by Paolo A. Ascierto, of Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, focused on treatment of cancer patients with COVID-19.
“It’s important to be cautious and not panic, we need to keep everybody safe, patients and physicians—and we can use drugs that we normally use in oncology to treat the cytokine storm. This treatment will be essential for these patients,” Ascierto said.
Data from Spain
At the Octubre University Hospital in Madrid, 90 of cancer patients admitted to the hospital had been treated for the disease. Carlos Gomez-Martin, of Octubre University Hospital, found that lung, gastrointestinal, and breast were the three most common cancers in 63 observed cancer patients with COVID-19.
Martin presented on the abstract Adapting oncologic practice to COVID19 outbreak: From outpatient triage to risk assessment for specific treatment in Madrid, Spain. Of these 63 cancer patients with COVID-19, 52 (82%) had metastatic disease, and 11 (18%) had non-metastatic cancer.
Thirty six patients (58%) were on active chemotherapy, 17 (26%) were on other treatment, and eight (12%) were receiving immunotherapy.
A total of 16 patients (25%) died of COVID-19, with a mean overall survival of 12.4 days. Thirty four (54%) patients developed respiratory failure, and 24 patients (38%) experienced acute respiratory distress syndrome—66% of patients who developed ARDS died.
What does it all mean?
These limited studies provide new information for how oncologists should treat their cancer patients who test positive for COVID-19, but the data are nowhere close to definitive.
“The further you go down into the subcategories, again, it is information that can help guide you, but it shouldn’t be the only information you follow or be significantly practice-changing,” Reckamp said to The Cancer Letter. “It’s helpful now that we’re getting some data from other centers around the world, so we understand some local issues.”
Although there are conflicts in the data—particularly the different outcomes for patients with cancer in China versus Europe—“overall, that data supports what we have been saying and what we have believed. And that is the cancer patients are at greater risk,” Lichtenfeld said to The Cancer Letter.
In the United States, the COVID-19 pandemic continues to peak at different times in different states, counties, and communities.
“We’re wondering how to integrate our desire to treat someone with the amount of immunosuppression it causes with the level of activity that’s in their community,” Merin said to The Cancer Letter. “In other words, it might be safe for us to do stem cell transplants in Los Angeles, but not in New York.
“How does a national board, a national body, give recommendations at a national level, when the conditions with the outbreaks are so variable across the country?”