Lindsay Fischer

Varying clinical trial site locations, offering more convenient times for follow-up, and improving research staff availability were some effective strategies to mitigate COVID-19–related patient concerns and to increase participation in international lung cancer clinical trials.

Flexible patient-focused approaches may increase clinical trial accessibility and enrollment in international lung cancer clinical trials beyond the COVID-19 pandemic, according Matthew P. Smeltzer, PhD, at a virtual press briefing during the International Association for the Study of Lung Cancer 2021 World Conference on Lung Cancer.

Findings, which evaluated international lung cancer clinical trial enrollment before and throughout the pandemic, showed a derived benefit from flexibility in “place” and “time” to increase trial participation.

More specifically, trial sites reported that the most effective strategies to mitigate COVID-19–related challenges included telehealth visits, remote diagnostics, remote patient-reported symptoms, and remote consenting alternatives to address issues associated with trial place. To achieve flexibility in time, the findings suggested allowing delayed assessments and visits, as well as Internal Review Board (IRB) changes.

“Overall, a more flexible approach [and] removing unnecessary barriers may improve enrollment and access to clinical trials, even beyond the pandemic,” Smeltzer said. Smeltzer is an associate professor of epidemiology and biostatistics at the School of Public Health at the University of Memphis in Tennessee.

The study examined enrollment data from 173 clinical trial sites and 171 trials across 45 countries. Data assessment included enrollment numbers from before the pandemic, in 2019, and during 2020 and 2021.

Significant disparities in enrollment were observed between 2019 and 2020. The average number of monthly trial enrollment decreased from 3.2 to 2.5 between April 2019 and April 2020. Similar changes were observed in May (3.4 to 1.8), June (3.1 to 1.5), July (3.2 to 1.7), and August (3.0 to 2.0).

The investigation considered results from a data collection survey that evaluated aggregate monthly enrollment for international lung cancer trials from 2019 to 2021, as well as from an action survey, which assessed the impact of COVID-19 on the conduct of clinical trials and identified mitigation strategies used.

“So where the [changes] are the most discrepant was at the beginning of the pandemic and April to August,” Smeltzer said. “But we see by September to December, the gap starts to close quite a bit. And it looks like, relative to 2019, monthly 2020 enrollment started to rebound despite the drastic increase and total COVID-19 cases diagnosed each month across the world.”

Investigators then put together a survey to better understand how the pandemic specifically impacted trial sites.

The surveys found that the most frequent site challenges included fewer eligible patients (67%), protocol compliance (61%), suspension of trials (60%), research staff availability (48%), and institutional closures (39%).

“Many trials were suspended,” Smeltzer noted. “And so that was a challenge. Availability of research staff was [also] a major challenge, and institutional closure. These are all challenges that were sort of at the institutional level.”

The surveys also provided insight into the challenges faced by patients themselves. Sixty-three percent of patients reported that a willingness to visit trial sites was a challenge to participation, 60% reported ability to travel as a challenge, and 52% reported access to trial site as a challenge. Forty percent of patients shared that an exposure-related quarantine impeded on their ability to participate in a trial, and 26% said that a COVID-19 infection prevented their participation.

In addition, fear of COVID-19 infection (83%), travel restrictions (47%), securing transportation (38%), and lab-radiology access (14%) made up the bulk of concerns patients had in relation to lung cancer clinical trials between 2020 and 2021.

To respond to these challenges and concerns, trial sites implemented a variety of mitigation strategies. Besides the most effective strategies mentioned above, common mitigation strategies included modified monitoring requirements (44%), telehealth visits (43%), labs at non–study facilities (27%), modified required visits (25%), and mail-order medications (24%).

“We asked them, ‘What were the most frequent mitigation strategies that they used? What did they do to try to improve the conduct of the trials both in terms of enrollment and compliance?’’’ Smeltzer said. “Modifying monitoring requirements was the No. 1 response, followed closely by telehealth visits.”

Other popular strategies involved radiology at non–study facilities (20%), altered trial schedules (19%), electronic consent processes (10%), and an altered consent process (7%).

“We think [there are] some good lessons learned here,” Smeltzer said.

He concluded by sharing that the results of this trial provide a good base assessment into the rigor needed to maintain the value and quality of clinical trials while also allowing flexibility to ensure that trials are feasible, accessible, and patient friendly. Furthermore, investigators are optimistic that the results of this assessment will continue to be beneficial beyond the COVID-19 pandemic.

Smeltzer MP, Bunn PA, Clark R, et al. Study of the impacts of COVID-19 on international lung cancer clinical trials. Presented at: International Association for the Study of Lung Cancer 2021 World Conference on Lung Cancer; September 8-14, 2021; virtual.

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Flexible patient-focused approaches may increase clinical trial accessibility and enrollment in international lung cancer clinical trials beyond the COVID-19 pandemic.

Convenient Clinical Trial Locations, Research Staff Availability Mitigate Barriers to Trial Access, Survey Says

Compared with a placebo, darolutamide (Nubeqa) demonstrated a similar safety profile in men with nonmetastatic castration-resistant prostate cancer (nmCRPC) continuing androgen-deprivation therapy (ADT), with comparable adverse event (AE) onset and occurrence rates, according to results from the ARAMIS trial presented during a poster presentation at the virtual 2021 ESMO Congress.

In the ARAMIS trial (NCT02200614), there was only a ≤2% difference in AE incidence of interest between the experimental and placebo group, and severity was low for both arms across 24 months. Fatigue was the only exception, with 12.6% of the darolutamide group who experienced the AE.

Notably, the incidence of rash was very low and nearly all cases of fatigue were reported early on in treatment. Most events were grade 1 or 2. The investigators noted that darolutamide poses a particular significance to the overall wellbeing of men with nmCRPC, given their potentially prolonged treatment time.

“Men with nonmetastatic castration-resistant prostate cancer are generally asymptomatic and may receive prolonged treatment with androgen receptor inhibitors (ARIs),” Christian Gratzke, MD, professor and chair in the Department of Urology at the Albert-Ludwigs-University in Freiburg, Germany, explained in a corresponding abstract presented alongside the poster. “Understanding the burden and time course of adverse events commonly associated with ARIs that may impact patients’ daily life will help inform optimal treatment selection for men with nmCRPC.”

Researchers analyzed the AEs most associated with antigen receptor inhibitors to provide patients with optimal treatment selection information. Kaplan-Meier estimates were utilized to analyze the incidence of AEs across the first 24 months. Time interval-specific analysis determined new event rates per each scheduled study visit.

Participants were randomized 2:1 to either receive darolutamide or placebo while continuing treatment with androgen deprivation therapy. The darolutamide group included 995 men, while the placebo group included 554.

Observed AEs across the darolutamide and placebo arms, respectively, included falls (0.2% vs 0.7%), fractures (0.4% vs 0.5%), mental impairment (0% vs 0.4%), hypertension (1.7% vs 1.1%), and rash (0.7% vs 0.2%).

Fatigue was reported by 12.6% of the men who received darolutamide, and by 8.3% of the placebo arm. Nearly half of all men who reported fatigue experienced it during the first month (5.9% vs 4.0%, respectively). The total rash incidences was 2.9% by 24 months. Half of all reported cases of rash appeared in the first 4 months, and almost all were grade 1 or 2. Serious AE incidence and initial onset were similar between the 2 groups.

Fatigue was shown to increase in cumulative incidence over time. In comparison, falls and fractures were mostly reported in the first month of treatment.

Hypertension onset was not specific to time interval. The number of cumulative incidences reported were similar across treatments. Although mental impairment was rare (<1% per treatment group), incidence occurrence was consistent across both groups.

While most cases of rash were grade 1 or 2, there were 2 patients who reported a grade 3 rash from the darolutamide group, and 1 patient who reported a grade 3 rash from the placebo group.

“The findings from this analysis confirm the safety profile of darolutamide showing a low incidence in a similar onset and cumulative incidence versus placebo,” Gratzke concluded.

Gratzke CJ, Fizazi K, Shore ND, et al. Time course profile of adverse events of interest and serious adverse events with darolutamide in the ARAMIS trial. Presented at: 2021 European Society Medical Oncology Congress; September 16-21, 2021’ Virtual. Abstract 630P.

Compared with a placebo, darolutamide demonstrated a similar safety profile in men with nonmetastatic castration-resistant prostate cancer (nmCRPC) continuing androgen-deprivation therapy, with comparable adverse event onset and occurrence rates. 

Lindsay Fischer | Authors

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Convenient Clinical Trial Locations, Research Staff Availability Mitigate Barriers to Trial Access, Survey Says

Comparable Safety Profile Seen With The Addition of Darolutamide to ADT Among Patients With nmCRPC