Evidence-Based Oncology June 2020
Evidence-Based Oncology June 2020
Joseph Alvarnas, MD
Interview by Maggie L. Shaw
Afsaneh Barzi, MD, PhD, and Sarmad Sadeghi, MD, PhD
David A. Fabrizio, BS
Maggie L. Shaw and Mary Caffrey
Conference Coverage: AACR, AMCP, ISPOR
Coverage by Gianna Melillo and Jared Kaltwasser
Joseph Alvarnas, MD
Conference Coverage: AACR, AMCP, ISPOR
Coverage from virtual meetings of the American Association of Cancer Research, the Academy of Managed Care Pharmacy, and the International Society for Pharmacoeconomics and Outcomes Research.
AACR: COVID-19 Increases Overall Risk of Death, Complications in Patients With Cancer, Study Shows
Patients with cancer who become infected with coronavirus disease 2019 (COVID-19) are far more likely to die or suffer severe complications than patients with COVID-19 who do not have cancer, according to new findings.
In a study released April 28, a team of researchers from China, Singapore, and the United States showed that patients with cancer who develop COVID-19 were more likely to develop in-hospital infections or chest distress, or spend time in the intensive care unit (ICU). Patients being treated with immunotherapy appear to be at particularly high risk. The results were published online in Cancer Discovery and reported at the virtual meeting of the American Association of Cancer Research.1
With a yearly estimate of 1.8 million new cancer cases for the United States in 2020, the patient population with compromised immune systems who could be affected by COVID-19 will only grow.2 The results were based on data collected through March, when 800,000 people in more than 200 countries had become infected with COVID-19, and there had been more than 40,000 deaths.1
As of April 28, more than 3 million people were infected worldwide, including 1“million in the United States; more than 214,000 have died, including more than 55,000 in the United States.3
The pandemic has left in its wake forced treatment delays, shuttered clinical trials, and decimated pain medication supplies, said Howard A. “Skip” Burris, MD, chief medical officer and executive director of the Sarah Cannon Research Institute and president of the American Society of Clinical Oncology. In a presentation to the virtual meeting of the Community Oncology Alliance, Burris called these challenges “daunting,” because they can be “devastating for patients with fast-moving or hard-to-treat cancers.”4
Fourteen hospitals from Wuhan, China, provided data for the randomized, controlled study of 641 patients enrolled between January 1, 2020, and February 24, 2020. There were 2 patient cohorts: patients without cancer who had COVID-19 (n = 536) and patients hospitalized with cancer and COVID-19 (n = 105). The mean ages were 64.00 and 63.50 years, respectively. They were matched by hospital, length of hospital stay, and age.
Overall, the patients with cancer fared worse compared with the patients without cancer, respectively, in number of in-hospital infections (19.04% vs 1.49%; P <.01) and smoking history (34.28% vs 8.58%; P <.01). In addition, there were more instances of chest distress in patients with both cancer and COVID-19 than among those with COVID-19 only: 14.29% versus 6.16% (P = .02).
Results were divided by clinical outcomes, cancer type, cancer stage, cancer treatment, and timeline of severe events. In these subcategories, patients with both cancer and COVID-19 fared worse across the board.
Clinical outcomes. The overall result in this subcategory was that the condition of patients with cancer and COVID-19 declined more rapidly than those with COVID-19 and no cancer. Specifically, they also had higher rates of the following:
• Death (odds ratio [OR], 2.34; 95% CI, 1.15-4.77; P = .03)
• ICU admission (OR, 2.84; 95% CI, 1.59-5.08; P <.01)
• At least 1 severe complication (OR, 2.79, 95% CI; 1.74-4.41; P <.01)
Cancer type. The most common cancers among patients with COVID-19 and cancer were lung (20.95%), gastrointestinal (12.38%), breast (10.48%), thyroid (10.48%), and hematological (ie, leukemia, lymphoma, myeloma) (8.57%). From this cohort, patients with hematological and lung cancers, respectively, fared the worst, with higher overall rates of death (33.33% and 18.18%), ICU admissions (44.44% and 27.27%), risk of severe/critical symptoms (66.67% and 50.00%), and possible use of invasive mechanical ventilation (22.22% and 18.18%).
Cancer stage. Cases of metastatic cancer (stage IV) in patients with COVID-19, compared with patients with nonmestatic cancer, led to overall higher risks for death (OR, 5.58; 95% CI, 1.71-18.23; P = .01), ICU admission (OR, 6.59; 95% CI, 2.32-18.72; P <.01), severe conditions (OR, 5.97; 95% CI, 2.24-15.91; P€<.01), and use of invasive mechanical ventilation (OR, 55.42; 95% CI, 13.21-232.47; P€<.01).
Cancer treatments. There were higher rates of death and chances of critical symptoms if patients with cancer and COVID-19 received immunotherapy: 33.33% and 66.67%, respectively. However, if these patients instead underwent surgery to treat their cancer, they had higher rates of ICU admission (37.50%) and use of invasive mechanical ventilation (25.00%).
Timeline of severe events. The principal measure here was hospital length of stay. The cohort with both cancer and COVID-19 had a 52.2% longer mean (SD)
hospital stay compared with the COVID-19–only group: 27.01 (9.52) days versus 17.75 (8.64) days. “Although COVID-19 is reported to have a relatively low death rate of 2% to 3% in the general population, patients with cancer and COVID-19 not only have a nearly 3-fold increase in the death rate than that of COVID-19 patients
without cancer, but also tend to have much higher severity of their illness.
Patients with cancer also have a 10-fold higher incidence of nosocomial SARS-COV-2 infections than patients without cancer. Altogether, these findings suggest that patients with cancer are a much more vulnerable population in the current COVID-19 outbreak,” the researchers concluded.
They suggested additional studies using a larger patient population, either from China or several countries, because data are still very limited on the patient population that has both cancer and COVID-19 and because the 3 continents with the highest rates of COVID-19 (Asia, Europe, North America) also have the highest incidences of cancer. Therefore, the results may not be generalizable.
1. Dai M, Liu D, Liu M, et al. Patients with cancer appear more vulnerable to SARS-COV-2: a multi-center study during the COVID-19 outbreak. Cancer Discov. Published online April 27, 2020. aacr.ent.box.com/s/2mh5713e6irjvcz6hb4c6y72bu1pljxq.
2. Cancer stat facts: common cancer sites. National Cancer Institute / Surveillance, Epidemiology, and End Results Program. Accessed April 29, 2020. seer.cancer.gov/statfacts/html/common.html.
3. Coronavirus Resource Center. Johns Hopkins University & Medicine. Accessed April 28, 2020. coronavirus.jhu.edu/us-map.
4. Shaw M. We must bring clinical trials to our communities, Burris says. The American Journal of Managed Care®. Published April 24, 2020. Accessed April 28, 2020. ajmc.com/conferences/coa2020/we-must-bring-clinical-trialsto-our-communities-burris-says.
AACR: Phase 3 EMBRACA Findings Suggest No Overall Survival Benefit With Talazoparib in Advanced BRCA-Mutated Breast CancerData from the phase 3 EMBRACA trial presented April 27 at the American Association for Cancer Research annual meeting indicated that the PARP inhibitor talazoparib exhibited no statistically signifi cant benefi t in the secondary end point of overall survival (OS) in patients with metastatic HER2-negative breast cancer and mutations in the BRCA1/2 genes. However, OS findings may have been understated, as most patients included in the study went on to receive subsequent systemic therapies.1
EMBRACA is the largest trial to date examining PARP monotherapy in patients with germline BRCA-mutated, HER2-negative advanced breast cancer. Previously, the trial’s primary analysis found that patients treated with talazoparib experienced signifi cantly prolonged progression-free survival (PFS) compared with chemotherapy (median PFS, 8.6 months vs 5.6 months), which led to its FDA approval in 2018.
While PFS was substantially benefi ted by talazoparib, OS can prove a challenge for patients with metastatic breast cancer due to the availability of numerous treatment options, said Jennifer Litton, MD, professor of breast medical oncology at MD Anderson Cancer Center, who presented results during AACR.2 The trial randomized 431 patients (2:1) with locally advanced or metastatic HER2-negative breast cancer and hereditary BRCA1/2 gene mutations to receive either talazoparib
(nš=š287) or physician’s choice of treatment of singleagent therapy (n = 144), including capecitabine, eribulin, gemcitabine, or vinorelbine.
In the trial, nearly half of patients in the talazoparib group received a subsequent PARP inhibitor or platinum therapy compared with almost 60% of patients in the chemotherapy group. When stratifi ed for only those receiving PARP inhibitors, approximately one-third of patients in the chemotherapy group received a subsequent PARP inhibitor compared with only 4.5% of those administered talazoparib.
The subsequent treatments provided were highlighted by Litton as she described how they may have potentially infl uenced results. In fact, after carrying out 2 sensitivity analyses to account for subsequent PARP inhibitor and/or platinum therapy, data suggest that the OS analysis underestimated the treatment benefit of talazoparib.
Aligned with findings from the primary analysis, patient-reported quality-of-life measures were improved among those administered talazoparib compared with chemotherapy as shown by a prolonged time to deterioration of overall health (26.3 months in the talazoparib group vs 6.7 months in the chemotherapy group).
“Talazoparib remains an option for patients with advanced breast cancer and a germline BRCA mutation due to its improvements in progression-free survival,” said Litton. “Other advantages include it being an oral once-daily option, as well as [the] improvements in quality of life [it] demonstrated.”
1. Litton JK, Hurvitz SA, Mina LA, et al. CT071: talazoparib (TALA) in germline BRCA1/2 (gBRCA1/2)-mutated human epidermal growth factor receptor 2 negative (HER2–) advanced breast cancer (ABC): final overall survival (OS) results from randomized phase 3 EMBRACA trial. Abstract presented at: American Association of Cancer Research Virtual Annual Meeting; April 27-28, 2020. https://www.abstractsonline.com/pp8/#!/9045/presentation/10773
2. Study finds no overall survival benefit, but improved quality of life with talazoparib in advanced BRCA-mutated breast cancer. News release. EurekAlerts. April 27, 2020. Accessed April 29, 2020. eurekalert.org/pub_releases/2020-04/uotm-sfn042420.php
AMCP: COVID-19 Upends Drug Purchasing Patterns, and More Disruption Likely, IQVIA Expert SaysThe global pandemic of coronavirus disease 2019 (COVID-19) has wreaked havoc on every part of the pharmaceutical business, from purchasing patterns to drug launches, and the upheaval will continue when Medicaid enrollment booms, according to an industry expert.
Douglas M. Long, MBA, vice president of industry relations for IQVIA, surveyed the pandemic’s eff ects on April 20, 2020, as he kicked off AMCP eLearning Days, a webinar series held in place of the annual meeting of the Academy of Managed Care Pharmacy (AMCP), which was canceled due to COVID-19.