Cancer clinical trials have long had a disparity problem, but a new push for more equitable trials that are both diverse and open to patients with certain health conditions seems to be finally paying off, per new research released at the 2022 annual meeting of the American Society of Clinical Oncology, or ASCO.
Fred Hutchinson Cancer Center biostatistician and health services researcher Dr. Joe Unger, whose research focuses on examining barriers and disparities in access to clinical trials, presented the first evidence showing that an ongoing campaign by ASCO, the Friends of Cancer Research (FoCR) and the U.S. Food and Drug Administration to modernize trial eligibility criteria has resulted in what he termed “a shift in patterns of exclusion criteria related to brain metastasis for patients with advanced cancers.”
Exclusion criteria are factors such as age, BMI, disease status, previous lines of treatment or presence of other health conditions such as HIV, pregnancy, diabetes, etc. that make someone ineligible to participate in a trial.
Unger’s work, done in conjunction with Hutch colleagues Drs. Riha Vaidya and Hong Xiao, plus Dr. Dawn Hershman, director of breast oncology at the Herbert Irving Comprehensive Cancer Center at Columbia University, was one of nearly two dozen Hutch studies shared at ASCO’s event, which in nonpandemic years attracts around 40,000 clinicians, researchers, pharmaceutical executives and patient advocates to Chicago’s McCormick Place Convention Center.
This year’s event, held June 3 through 7, was hybrid, with attendees joining in person and virtually from all over the world. The theme for ASCO 2022 was “Advancing Equitable Cancer Care Through Innovation” and Hutch researchers delivered in spades, with new findings on clinical trial eligibility, the impact of Medicaid’s expansion on cancer patients, biosensors to track treatment side effects and more.
Trials enroll more brain mets patients
For the study evaluating the effect of broadened trial eligibility criteria, Unger and associates used ClinicalTrials.gov, the National Cancer Institute’s database of U.S. investigational drug studies, to find cancer trials initiated between January 2013 and October 2021 that recruited patients with metastatic colorectal, lung or breast cancer. Metastatic cancer has spread from its original location to other parts of the body, such as the lungs, liver, bones, brain or other sites.
For each trial, they determined if patients with brain metastasis, or “mets,” were not excluded (able to join the trial); conditionally excluded (able to join in some circumstances) or wholly excluded (barred from the trial due to the presence of brain mets). Most of the trials were Phase 2 (trials which determine how well a drug or intervention works in patients); more than 10% were Phase 3 trials, which compare a new intervention with standard treatment. The majority of the trials examined were sponsored by the pharmaceutical industry.
Researchers examined trials both before and after the three organizations in 2017 released recommendations that cancer trial eligibility criteria, including those related to brain metastases, be broadened to make these trials more inclusive. Previous research by Unger has shown that structural and clinical barriers keep three out of four cancer patients from participating in trials.
All told, the researchers evaluated nearly 2,000 cancer clinical trials and found significant changes since the recommendations went into effect.
“Following the transition period, there were more trials where patients with brain metastasis were not excluded and fewer trials where patients with brain metastasis were conditionally excluded,” Unger said during his podium presentation.
The researchers estimated how the recommendations changed the proportion of clinical trials that would not exclude patients with brain mets. After the recommendations, 15.6% of trials did not exclude these patients, whereas only 9.2% would not have excluded them if the recommendations hadn’t been made, the researchers estimated.
“That’s a statistically significant finding,” Unger said, adding that the estimated proportion of trials in which patients with brain metastasis were conditionally excluded decreased from 85.3% to 76.9%, which was also statistically significant (meaning the results are not likely to be due only to chance).
While there was no difference in the proportion of trials in which patients with brain mets were wholly excluded, Unger said their research showed there was a trend toward fewer exclusions.
“Our findings indicate that patients with brain metastasis in advanced cancer trials for breast, lung and colorectal cancers are rarely wholly excluded,” Unger said. “Most trials conditionally exclude patients with brain metastasis. Overall, though, the ASCO/FoCR/FDA recommendations appear to be associated with a shift in the patterns of eligibility criteria. More trials than expected now don’t exclude patients with brain metastasis.”
Unger said it was the first evidence that cancer clinical trials have become more inclusive to a broader set of patients in response to the recommendations.
“More inclusive eligibility improves trial access and representativeness and increases the pace at which trials can enroll, which hastens new treatment discovery for all patients,” he said. Unger also said he hopes to do additional analysis regarding other eligibility changes made by the organizations.
“It’s important to continue to evaluate the impact of these recommendations,” he said.
Medicaid expansion helps cancer patients
In another podium presentation, Unger shared findings from another study, conducted through the SWOG Cancer Research Network, that examined how the Medicaid expansion that was offered to individual states as part of the Affordable Care Act, or ACA, has affected cancer patients.
The study also involved Xiao, Vaidya and Hershman along with biostatistician Dr. Michael LeBlanc, director of the SWOG Statistics and Data Management Center at the Hutch. It examined the number and the proportion of patients, ages 18 to 64, according to their insurance status at enrollment in cancer treatment trials using SWOG trial data.
Researchers looked at trial participants between April 1992 through February 2020, and whether these patients used Medicaid or private insurance. They examined the records of more than 51,000 patients; after an analysis, they found a 20% increase per year in the odds of patients using Medicaid after the ACA expanded it, a statistically significant finding.
Women tended to use Medicaid more than men (26% versus 8%). States that implemented Medicaid expansion in 2014 or 2015 increased Medicaid use by 27%; states that did not implement it increased Medicaid use by only 7%.
The SWOG team found that the implementation of the ACA’s Medicaid expansion “was associated with nearly a threefold increase in the proportion of patients using Medicaid in cancer clinical trials by early 2020,” as they wrote in their study.
Currently, all but 12 states have passed the ACA’s Medicaid expansion. Those without Medicaid expansion are Alabama, Florida, Georgia, Kansas, Mississippi, North Carolina, South Carolina, South Dakota, Tennessee, Texas, Wisconsin and Wyoming.
“These findings are important because improved access to clinical trials for Medicaid patients provides greater access to the newest treatments. And it’s critical for improving confidence in trial findings applied to all patients, including those who are socioeconomically vulnerable,” Unger said in his ASCO presentation.
He also said the Clinical Treatment Act, which went into effect in January 2022, and which mandates state-level Medicaid programs to cover the routine care costs of clinical trials for Medicaid patients, “may continue to improve access to clinical trials for socioeconomically underserved populations.”
No biopsies for recurrent breast cancer?
Also in conjunction with ASCO 2022, Dr. Poorni Manohar, a breast cancer oncologist at Fred Hutch and a researcher with the Hutchinson Institute for Cancer Outcomes Research, or HICOR, shared results from her study of real-world practice patterns in the diagnosis of recurrent metastatic breast cancer in Washington state.
National guidelines recommend that people who go on to develop metastatic recurrence after treatment for early-stage breast cancer undergo biopsy and biomarker testing to reassess and confirm the diagnosis. These cancers’ biological targets (think HER2 receptors or estrogen receptors), which often direct treatment, can change as the cancer progresses and takes on new mutations. Early-stage patients with estrogen-receptor positive breast cancer may become estrogen-receptor negative with metastatic recurrence, and so on.
Manohar and her colleagues in HICOR drilled down into cancer diagnosis data from the Washington state cancer registry and insurance claims data from private insurers (Premera, Regence) and public insurers (Medicare, Medicaid) to determine if patients were receiving care that followed national treatment guidelines or if there were disparities in cancer care and guideline adherence.
The researchers looked at breast cancer patients 18 and older who had experienced metastatic breast cancer recurrence or a new metastatic diagnosis after early-stage treatment. They identified 715 patients with recurrent mets of any biological subtype (HER2-positive receptors or not, ER-positive receptors or not, etc.). Most of the patients were white women and the majority lived in metropolitan neighborhoods. Around 13% of patients lived in areas of high socioeconomic deprivation, according to the Area Deprivation Index.
Manohar and colleagues found that only about half of the patients diagnosed with recurrent mets received a biopsy to confirm the metastatic diagnosis. Further, only about half of these patients underwent biomarker reassessment. Both biomarkers and biopsies are used to accurately characterize the cancer and its potential biological targets. Patients with the highest comorbidity index score, meaning patients with the worst health, were more likely to undergo biopsy confirmation than those without. High-volume cancer centers conducted biopsy more often than low-volume cancer centers.
Why does this study matter?
“This is important because all of our treatment paradigms in metastatic breast cancer are framed around hormone and HER2 status,” Manohar said. “If there is a change from the primary tumor — and this can occur up to 20% of the time — this dramatically alters our treatment recommendations, response to therapy, and may impact survival.”
Tracking side effects with wearables
Anti-nausea drugs and other supportive cancer medications have been game-changers for patients going through chemotherapy, helping them complete treatment without health complications like infection, excessive vomiting or other incapacitating side effects.
Still, half of the nearly 370,000 cancer patients in the U.S. who receive chemotherapy have to go to the emergency room or stay in the hospital unexpectedly each year due to poorly controlled symptoms or treatment side effects.
How do we fix that? Researchers with Fred Hutch’s HICOR group have initiated a study that will use both a smartphone app and a wearable biosensor smartwatch to help identify patients who may be at a higher risk for an ER or hospital visit. HICOR co-directors Drs. Scott Ramsey and Veena Shankaran are principal investigators.
Details of the forthcoming trial were presented as a poster at ASCO’s 2022 meeting and simultaneously published in the Journal of Clinical Oncology. The new study enrolls patients ages 18 to 80 who have a biopsied solid tumor (in other words, no lymphomas or leukemias) and are scheduled to receive their first IV or oral cancer therapy as an initial or a new line of treatment.
Open to both early-stage and metastatic patients, the trial asks participants to wear their biosensor daily and complete surveys (surveys will be in English for this first trial) that capture patient-reported outcomes, such as fatigue, nausea/vomiting, fever, diarrhea, etc. Patients who receive anti-hormone therapy and/or radiation without chemotherapy are not eligible for the trial.
The study will have two phases. The vanguard phase will enroll 30 patients for a two-week trial run; a second, operational phase, enrolling 70 patients, will launch later.
“The vanguard sample size allows for the recruitment of around 10 patients at each of the three participating oncology community clinics, which is standard for initial device and software testing and development,” said HICOR’s Karma Kreizenbeck, lead author on the study.
Kate Watabayashi, senior project manager for HICOR, said the trial should be relatively easy for participants.
“The smartwatch passively collects things like vital signs, and the app has a symptom survey that patients are asked to complete daily during the study period,” she said. “Phase one is where we are assessing feasibility and usability of the biosensor and the app.”
The vanguard phase will evaluate patient recruitment, completeness of data capture, app usability and user satisfaction with the biosensor, among other things. The operational phase aims to confirm the vanguard findings in a larger sample of patients and validate data such as patient-reported information regarding hospital visits.
“Data collected from the vanguard will inform modifications to the app for the operational phase,” Kreizenbeck said, adding the operational phase will include enough patients that the researchers will be able to test it out in both low-volume and high-volume treatment centers as well as those in rural and urban settings.
“The hope,” Watabayashi explained, “is that we can eventually develop a wearable sensor and app combination that would help patients monitor their symptoms during chemotherapy and communicate with their care teams to avoid unnecessary emergency department or in-patient hospital visits during treatment.”
Funding for the study of eligibility criteria was provided by the Fred Hutch Public Health Sciences Division. Funding for the study of the effect of Medicaid’s expansion on cancer clinical trials was provided by the NIH/NCI, an American Cancer Society Research Scholar grant and The Hope Foundation for Cancer Research. Funding for HICOR’s real-world practice patterns study was provided by the Conquer Cancer Foundation of ASCO and Pfizer, and funding for HICOR’s wearables study was provided by F. Hoffmann-La Roche Ltd./Genentech, Inc.