“Basket” studies — another new class of clinical trial


Although it has no immediate relevance to the treatment of prostate cancer, it is worth noting that the results of the very first, completed and published “basket” type of clinical trial appear in this week’s issue of the New England Journal of Medicine (NEJM).

So what on Earth is a “basket” study?

Basically, a “basket” study is a new type of clinical trial designed to investigate how patients respond to drugs (or presumably other forms of treatment) based — in the case of cancers — not on the organ in which their disease originated but on the specific mutations in the patients’ tumors regardless of where the cancer originated.

The study by published by Hyman et al. in this week’s NEJM looked at the effects of a drug called vemurafenib (Zelboraf®) in the management of a total of 122 patients with BRAF V600 mutation-positive, non-melanomatous cancer (including 27 patients with colorectal cancer who received vemurafenib and cetuximab). Basically this means that it included patients who all expressed the BRAF V600 gene mutation, but none of whom had the aggressive form of skin cancer known as melanoma. (Vemurafenib has already been approved for the treatment of patients with melanoma, and so that is why patients with melanoma were left out of this study.)

This was still a relatively small, Phase II trial, and because it wasn’t specific to prostate cancer in any way (because the BRAF V600 gene appears to be irrelevant in the management of prostate cancer), we’re not going to worry about the details. Readers who are interested in the details can look at the study abstract on the NEJM web site or this media release from Memorial Sloan-Kettering Cancer Center. Suffice it to say that the authors conclude that

BRAF V600 appears to be a targetable oncogene in some, but not all, non-melanoma cancers.

What is interesting about this study from a prostate cancer perspective is that it is studies of this type that will allow us to gain early insights into whether certain types of approved and unapproved, genetically targetable drugs may have value in the management of prostate cancer as one of several cancers known to be affected by expression or non-expression of specific genes.

As with the so-called “N-of-1″ trials discussed on this web site the other day and the STAMPEDE type of trial that recently confirmed the long-term benefits associated with early use of combination treatment with ADT + chemotherapy for men newly diagnosed with metastatic prostate cancer, these types of “basket” trial are a further interesting exploration of new types of clinical trial that will support growing research into “precision” and “individualized” medicine over time. We need to be aware of this type of trial for this reason, and to be on the look out for data form any such trial that does include prostate cancer patients as part of the patient “basket” associated with a specific, targetable gene.

6 Responses

  1. Good marketing by MSK coining their name for targeted therapy based on DNA alterations. Maybe this approach will one day unravel the common threads between all cancers.

    However, as the audience on this forum knows, the challenge with prostate cancer is that we may have many buckets, so IMHO opinion we need something that cuts across the heterogeneity of this disease. Perhaps future immune therapy.

  2. Dear Dominic:

    (1) Prostate cancer is a long way from being the only cancer that has a high level of heterogeneity. Just as one example, there are probably at least 40 or 50 forms of lymphoma identified to date, and there may be a lot more.

    (2) Just as we now know that “cancer” isn’t one disorder, but probably comes in several hundred subtypes, we are also aware that finding forms of therapy that “cut across the heterogeneity” of cancer in general is extremely unlikely (just as we don’t have forms of therapy that cut broadly across subtypes of infection).

    (3) I am not aware of any good reason today to believe that we will find any form of therapy in the future that will “cut across the heterogeneity” of prostate cancer in particular. On the other hand, it is possible that we will find therapies that will work across the relative homogeneities of genetically driven subtypes of cancer, and we have already seen that this is the case for some of these subtypes.

  3. Don’t get me wrong , if we can cut across some “homogenic” subtypes across various cancers it’s not a bad thing.

  4. Dominic:

    Also, MSKCC didn’t, as far as I know, coin the term “basket” studies for this type of clinical trial. It’s been around for a few years now. So I am not at all sure what you were implying by your statement about “Good marketing by MSK coining their name for targeted therapy based on DNA alterations.” The term “basket” studies only refers to a type of trial. It has nothing to do with anything going on exclusively at MSKCC.

  5. From what I have seen they have been the institution to promote the term in WSJ and other venues. Not implying there is anything wrong with it.

  6. Dominic:

    Well they were the lead group that organized the study, but they didn’t do anything that anyone else doesn’t do when they are the lead organization for a major study.

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