publication date: May. 8, 2020

Clinical Roundup

Cancer patients without insurance or Medicaid don’t experience the same benefits of clinical trials

Cancer patients with no health insurance or those enrolled in Medicaid see smaller survival benefits from experimental therapies in clinical trials, according to a study published April 30 in JAMA Network Open.

The SWOG Cancer Research Network study is the first to examine whether treatment effects from randomized cancer clinical trials with positive findings apply to important demographic and insurance subgroups. The finding that cancer clinical trial patients with no or low insurance do not get the same benefits of experimental therapies as patients with private insurance—regardless of sex, age or race or ethnicity—supports efforts in Congress to expand insurance coverage.

These efforts include the Clinical Treatment Act, a bipartisan bill introduced in February in the House of Representatives that guarantees coverage of the routine care costs of clinical trial participation for Medicaid enrollees with a life-threatening condition. Nearly 20% of Americans receive health insurance through Medicaid.

The American Society of Clinical Oncology, the American Cancer Society, and the American Medical Association support the bill.

“A patient’s insurance coverage seems to be related to the extent to which they benefit from new experimental treatments tested in trials,” study lead Joseph Unger, a SWOG health services researcher and biostatistician based at Fred Hutchinson Cancer Research Center, said in a statement. “Our findings highlight the importance of policies that would provide more Americans insurance coverage, and underline the importance of improving that coverage.”

Unger and his team examined data from 19 SWOG phase III randomized treatment trials that enrolled patients between 1984 and 2012 and followed those patients up to five years after their trial treatment. The 19 trials tested drugs for a number of cancers, including breast and lung.

The analysis included 10,804 patients. The team then assessed whether the overall survival rates, progression- or relapse-free survival rates, differed by age, sex, race and ethnicity, and insurance status.

Patients 65 or older, younger than 65, male, female, minority, non-minority, and with private insurance who received experimental trial drugs all, on average, lived longer compared to patients who received standard treatment. Uninsured patients or those enrolled in Medicaid did not have a strong survival benefit.

“People with fewer financial resources have access to fewer healthcare resources, which can have a persistent, negative influence on their health,” Unger said. “Patients in trials having no or limited insurance may not have the financial means to pay for the extra supportive treatments or post-trial cancer treatments that help people live longer. This could be especially meaningful for understanding treatment benefits if experimental therapy requires more supportive care or is more difficult to adhere to than standard treatment.”

The SWOG study was funded by the NIH through NCI grant awards CA189974, CA180888, CA180819. The Hope Foundation for Cancer Research also supported the study through a Dr. Charles A. Coltman Jr. Fellowship Award to Unger, as well as direct funding to the SWOG Statistics and Data Management Center based at Fred Hutch, funding which supports research infrastructure, trial design, and data analysis.

Along with Unger, the SWOG team includes Charles D. Blanke, of Oregon Health & Science University, the SWOG group chair; Michael LeBlan, of the SWOG Statistics and Data Management Center and Fred Hutch, the SWOG group statistician; William Barlow, of the SWOG Statistics and Data Management Center and Fred Hutch; Riha Vaidya, of the SWOG Statistics and Data Management Center and Fred Hutch; Scott D. Ramsey, of Fred Hutch; and Dawn L. Hershman, of NewYork-Presbyterian/Columbia University Irving Medical Center, and the SWOG vice chair for NCORP research.

 

Libtayo shows clinically-meaningful and durable responses in second-line advanced basal cell carcinoma

Libtayo (cemiplimab) demonstrated clinically meaningful and durable responses in patients with advanced basal cell carcinoma who had progressed on or were intolerant to prior hedgehog pathway inhibitor therapy.

Libtayo is being jointly developed and commercialized by Regeneron and Sanofi under a global collaboration agreement. Regeneron and Sanofi said they plan regulatory submissions in 2020.

Approximately 20,000 U.S. patients have advanced BCC, and it is estimated that about 3,000 die each year. BCC marks the second non-melanoma skin cancer for which Libtayo has demonstrated first-in-class data and follows its initial U.S. approval in advanced cutaneous squamous cell carcinoma in 2018.

In the trial phase II, the objective response rate for patients (n=84) with locally advanced disease was 29% (95% CI: 19%-40%), with an estimated duration of response exceeding one year in 85% of responders. The durable disease control rate (DCR–response or stable disease lasting at least six months) was 60% (95% CI: 48%-70%). In a preliminary analysis of patients (n=28) with metastatic disease, the ORR was 21% (95% CI: 8%-41%), with an estimated DOR exceeding one year in 83% of responders. The durable DCR was 46% (95% CI 28%-66%). All data were assessed by an independent central review.

“These data in advanced BCC provide the third instance where Libtayo monotherapy has demonstrated robust and clinically meaningful outcomes in advanced cancer, and follows last week’s announcement in advanced non-small cell lung cancer where the pivotal trial was stopped early for positive overall survival,” Israel Lowy, senior vice president of Translational and Clinical Sciences, Oncology, Regeneron, said in a statement.

There were no new safety signals in this trial. Among the 132 patients assessed for safety (84 locally advanced and 48 metastatic), 95% experienced an adverse event (AE), 32% had a serious AE and 13% discontinued due to an AE. There were 10 deaths in the locally advanced group and nine deaths in the metastatic group; none of the deaths were considered treatment-related.

“While PD-1 inhibitors have transformed the outlook for many patients with melanoma, progress for patients with non-melanoma skin cancers has not been as rapid,” said Peter C. Adamson, global head of Oncology Development at Sanofi. “We are continuing to address this unmet need by first bringing Libtayo to patients with advanced cutaneous squamous cell carcinoma, and now, with this second trial, as a potential therapy for patients with advanced basal cell carcinoma. These important new results further demonstrate Libtayo’s potential in patients with difficult-to-treat, non-melanoma skin cancers.”

In this ongoing, global phase II trial, patients received Libtayo 350 mg intravenously every three weeks for up to 93 weeks or until disease progression, unacceptable toxicity, withdrawal of consent or confirmed complete response. ORR is the primary endpoint and key secondary endpoints include overall survival, progression-free survival, duration of response, safety and quality of life.

 

New tumor sampling method significantly improves genetic testing for cancer treatment

A holistic tumor sampling method that more accurately detects genetic alterations in tumors has been developed by researchers from the Crick, Roche and The Royal Marsden NHS Foundation Trust. The study was published in Cell Reports.

Initially, the researchers tested improved sampling in lung and bladder cancers, where a simulation of improved sampling reduced misclassification rates in deciding whether a patient was suitable for immunotherapy from 20% to 2% and from 52% to 4% respectively, when compared to current methods.

Based on this finding, the researchers developed a technique called representative sequencing, which builds a more accurate picture of a tumor’s DNA. This works by taking the majority of the tumor removed at surgery—tissue that is not currently sampled and is routinely discarded—and mixing it so that cells from different areas of the tumor are more evenly distributed. A sample is then taken from this mixture to be DNA sequenced.

The researchers tested the method in 12 patients with kidney, breast, colon, lung or skin cancer. Comparing new and current methods, they found that representative sequencing gave far more consistent results, as it avoids the bias of looking at just one small part of the tumor tissue. The new method captures information from a well-mixed representation of the whole tumor.

The method is being further tested in 500 tumors at The Royal Marsden in London to determine its feasibility and utility.

“By equipping clinicians with more accurate information about a tumor, we hope our method will lead to patients and treatments being significantly better matched. Additionally, there is an opportunity for critical biological insights to be made by increasing the search space within each tumor,” Samra Turajlic, group leader at the Crick and consultant medical oncologist at The Royal Marsden, said in a statement.

Through extensive testing on a case of kidney cancer, the representative sampling method gave identical genetic results 95% of the time, compared to only 77% consistency with the current methods. Similarly, in a case of skin cancer, the new method correctly identified a highly complex and difficult to treat cancer from the outset, whereas the current method missed important genetic information.

“This method is more accurate, has more reproducible results and has the same sequencing cost as the current technique. In fact, by introducing an extra, simple purification step, it could become much cheaper than the existing process. It could be a gamechanger for tumor sampling in hospitals and in research,” Kevin Litchfield, lead author and bioinformatician in the Translational Cancer Therapeutics Laboratory at the Crick, said in a statement.

Copyright (c) 2020 The Cancer Letter Inc.