Basket Studies: An Innovative Approach for Oncology Trials


Basket studies can be useful to determine if a drug targeting a certain genetic mutation at a particular site may be effective in treating that same genetic mutation found in cancer located in another site of the body.

Clinical trials in oncology have traditionally focused on the treatment of cancer at a certain location in the body, such as lung or breast cancer. It has become common for trials to focus on a specific genetic mutation at a particular location (i.e. ALK+ non-small cell lung cancer). A more recent development for oncology clinical trials is known as a basket study, and includes patients with a certain genetic mutation in common regardless of the site or origin of cancer in the body.

Patients in a basket study have the same genetic mutation (i.e. TRK+), but include cancer at a variety of sites, such as lung, breast, prostate, etc.1 Basket studies are sometimes referred to as bucket studies and have also been described as 'tissue agnostic' or 'pan-tumor' studies.2

Basket trials can be relatively simple in design to include specific treatment arms or 'baskets' for cancers of different origins or locations. The design can also become more complex with the baskets including more than 1 genetic mutation across multiple cancer locations or they may be designed to evaluate multiple drugs across a selected number of genetic mutations, and cancer locations.3

Basket studies can be useful to determine if a drug targeting a certain genetic mutation at a particular site may be effective in treating that same genetic mutation found in cancer located in another site of the body. An example is vemurafenib (Zelboraf), which was originally approved by the FDA in 2011 for the treatment of melanoma with BRAF V600E genetic mutation. A basket study was conducted involving patients with BRAF genetic mutation, and it was determined that vemurafenib was also effective in treating a rare blood cancer known as Erdheim-Chester Disease (ECD), where patients have BRAF V600 genetic mutation. This basket study helped lead to the eventual FDA approval for vemurafenib to treat BRAF+ ECD in 2017.1

As of March 14, 2018, there were 37 basket studies found on Of this total, only 2 were clearly intended to be used for FDA submission. Another 9 trials were considered potentially able to be used for FDA filing. The remaining 26 studies were classified as exploratory, and believed to be too early in the developmental process to be considered for FDA filing as a pivotal study.2

The most common use for basket studies has been a technique for early or midstage clinical trial research to help evaluate which potential indications for a drug would be good candidates for larger trials with a more specific target, in terms of origin or location of cancer. However, in a fairly recent case, the FDA has considered a basket study to be adequate evidence for approval. In May 2017, pembrolizumab (Keytruda) was approved for an expanded indication to treat microsatellite instability-high cancer based only on genetic abnormality, regardless of origin or site of cancer.3

Larotrectinib, developed by Loxo Oncology, is positioned to potentially become the first FDA approval as a new drug to be based on the results of a basket study. It’s currently under review by the FDA for the treatment of TRK+ genetic mutation regardless of origin or site of cancer. In the pivotal basket study, it demonstrated impressive efficacy results with an 75-80% overall response rate (ORR). The Prescription Drug User Fee Act (PDUFA) date for larotrectinib is November 26, 2018.4

Some strengths of basket studies are that they can be efficient in identifying effective treatments for cancers at multiple sites with a common genetic mutation. If a drug is already approved for treating cancer with a specific genetic mutation at 1 location, a basket study can be useful to see if the efficacy translates to cancer at other locations in the body. Additionally, only 1 genetic assay is required for screening patients for study enrollment.5

Some weaknesses of basket studies are that they may have small sample sizes, particularly if the genetic mutation is rare. Basket studies may not include a comparator arm, so it can be difficult to interpret efficacy. There may be also be difficulties in distinguishing prognostic aspects, information about a patient’s overall cancer outcome, from predictive aspects, which involves information about the impact of treatment.5

It will be interesting to see if basket studies increase in popularity in the future, both for exploratory purposes or as a pivotal studies for FDA submission to gain approval for new drugs. After approval, getting prescribers to perform the appropriate test to identify the genetic mutation for which the drug is approved will be an important consideration. This may be a challenging task, particularly if the genetic mutation is rare and not typically evaluated in current regularly used genetic tests.


  • Tao JJ, Schram AM, Hyman DM. Basket Studies: Redefining Clinical Trials in the Era of Genome-Driven Oncology. Annu. Rev. Med. 2018. 69:319—31.
  • Dubuque C, Major P, Suarez, et al. Oncology Basket Trials: An Emerging Paradigm Shift in Trial Design & Treatment Approach. Trinity Partners. May 2018.
  • Cunanan KM, Gonen M, Shen R, et al. Basket Trials in Oncology: A Trade-Off Between Complexity and Efficiency. Journal of Clinical Oncology, Vol 35, No 3 (January 20), 2017: pp 271-273.
  • Drilon A, Laetsch TW, Kummar S, et al. Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med 2018;378:731-9. DOI: 10.1056/NEJMoa1714448.
  • Polley E. Basket and Umbrella Trial Designs in Oncology. Dose Selection for Cancer Treatment Drugs. Stanford Medicine. May 2017.

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