Pathologists can be paid for their role in identifying and recruiting patients for basket studies and reporting results of medical laboratory tests

Anatomic pathologists who biopsy, report, and diagnosis cancer will benefit from a better understanding of basket studies and their application in developing cancer treatment therapies. Such studies can lead to more documentation of the effectiveness of various therapies for cancers with specific gene signatures

The US National Library of Clinical Medicine defines basket studies as “a new sort of clinical studies to identify patients with the same kind of mutations and treat them with the same drug, irrespective of their specific cancer type. In basket studies, depending on the mutation types, patients are classified into ‘baskets.’ Targeted therapies that block that mutation are then identified and assigned to baskets where patients are treated accordingly.”

Also known as basket or bucket trials, basket studies involve patients who have different cancers at a various sites, such as lung, breast, and prostate, but whom share a common genetic mutation, explained Ryan Chandanais, MS, CPhT, Emerging Therapeutics Analyst at Diplomat Pharmaceuticals, Flint, Mich., in an article he penned for Pharmacy Times titled, “Basket Studies: An Innovative Approach for Oncology Trials.”

The popularity of basket studies has increased in tandem with genomic medicine’s rise, stated an article in Cancer Therapy Advisor titled, “Wider Use of Basket Trials Could Hasten Development of Precision Therapies.”

“Historically, cancer clinical trials have been centered on the treatment of cancer based on the anatomic location in the body, like breast cancer or brain cancer or lung cancer. A basket study is a novel trial design that includes patients with a certain molecular aberration regardless of location or tissue of origin of cancer in the body. The genomic revolution in oncology has fueled these studies,” Vivek Subbiah, MD, Associate Professor and Medical Director, Clinical Center for Targeted Therapy ( Phase 1 trials program), at the University of Texas MD Anderson Cancer Center in Houston, told Cancer Therapy Advisor. (Photo copyright: MD Anderson Cancer Center.)

Basket Studies Get Results

During a basket study, researchers may find that a drug’s effectiveness at targeting “a genetic mutation at one site can also treat the same genetic mutation in cancer in another area of the body,” noted Pharmacy Times, which also pointed out basket studies are often starting points for larger oncology trials about drugs.

For example, it was a basket study which found that vemurafenib (marketed as Zelboraf), intended for treatment of V600E, a mutation of the BRAF gene, may also treat Erdheim-Chester disease (a rare blood disorder) in patients who have the BRAF V600 gene mutation, Pharmacy Times reported.

Additionally, the US Food and Drug Administration’s approval of the cancer drug Vitrakvi (larotrectinib), an oral TRK inhibitor, marked the first treatment to receive a “tumor-agnostic indication at time of initial FDA approval,” a Bayer news release stated. The drug’s efficacy, Pharmacy Times noted, was found in a “pivotal” basket study.

Basket Studies, a Master Protocol Trial Design

The basket study technique is an example of a master protocol trial design. The FDA defines a master protocol as “a protocol designed with multiple substudies, which may have different objectives and involves coordinated efforts to evaluate one or more investigational drugs in one or more disease subtypes within the overall trial structure. A master protocol may be used to conduct the trial(s) for exploratory purposes or to support a marketing application and can be structured to evaluate, in parallel, different drugs compared to their respective controls or to a single common control.”

Other master protocols include umbrella studies and platform studies, according to Cancer Therapy Advisor, which noted that each master protocol trial design has its own unique objectives:

  • Umbrella studies look at the effectiveness of multiple drugs on one type of cancer;
  • Platform trials investigate the effectiveness of multiple therapies on one disease on an ongoing basis; and
  • Basket studies focus on the effectiveness of one therapy on patients with different cancers based on a biomarker.

“In contrast to traditional trials designs, where a single drug is tested in a single disease population in one clinical trial, master protocols use a single infrastructure, trial design, and protocol to simultaneously evaluate multiple drugs and or disease populations in multiple substudies, allowing for efficient and accelerated drug development,” states the FDA draft guidance, “Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics.”

Final FDA guidance on master protocols design is expected early in 2020, an FDA spokesperson told Cancer Therapy Advisor.

While master protocol studies show promise, they generally have small sample sizes, noted researchers of a study published in the journal Trials. And some researchers have ethical concerns about basket studies.

Scientist at the Jagiellonian University Medical College in Krakow, Poland, published a study in BMC Medical Ethics, titled, “Umbrella and Basket Trials In Oncology: Ethical Challenges,” in which they cite their concerns with basket studies, which are related to scientific validity, risk-benefit ratio, and informed consent.

Nevertheless, basket studies appear to hold promise for precision medicine. Anatomic pathologists may want to follow some of them or find a way to get involved through identifying clinical laboratory tests and reporting the results.

—Donna Marie Pocius

Related Information:

Basket Studies: An Innovative Approach for Oncology Trials

Basket Studies: Redefining Clinical Trials in the Era of Genome-Driven Oncology

Wider Use of Basket Trials Could Hasten Development of Precision Therapies

FDA Approves Vitrakvi (larotrectinib), the First Ever TRK Inhibitor for Patients with Advanced Solid Tumors Harboring an NTRK Gene Fusion

FDA: Design Strategies to Expedite Development of Oncology Drugs and Biologics Guidance for Industry

Systematic Review of Basket Trials, Umbrella Trials, and Platform Trials: A Landscape Analysis of Master Protocols

Basket Trials for Intractable Cancer

Umbrella and Basket Trials in Oncology: Ethical Challenges

Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics