“Basket Study” Targets Mutation Not Cancer Type, Widens Patient Drug Trial Access
Memorial Sloan Kettering Cancer Center (MSK) just published results in the New England Journal of Medicine for a basket study for an early Phase II study, led by MSK Physician-in-Chief and Chief Medical Officer José Baselga, that looked at the effect of vemurafenib (Zelboraf) in multiple nonmelanoma BRAFV600-mutated cancers in 122 patients from 23 centers around the world. What is unique about this design is it focused on mutation rather than histology. This makes it far more likely to pick up activity in a host of tumors with this mutation more quickly than a traditional trial schema, where each tumor and mutation would be tested individually.
Basket studies also have the ability to greatly increase the number of patients eligible to receive certain drugs. The mixed efficacy seen in this study proves that drugs can reach patients beyond the current approved use but, expectedly, do not work for everyone. As a pioneering trial, this data demonstrates the promising benefits of basket studies and the need for more work to be done with these types of trials. I personally think this marks the beginning of an era—faster lab-to-lifesaving runways for the future. It’s an exciting time, when patient outcomes will improve more rapidly than before, and personalized medicine is one step closer.
Commercially, this is a both a great opportunity and challenge for pharmaceutical manufacturers—more defendable niches. A double-edged sword: You may get a smaller slice of the pie, but you can have it all.
Opportunity to get their drugs to more patients faster. Think of a tollway with only one tollbooth and the line backed up versus one with 10 lanes where at least some of the tollbooths are moving faster than others. We may not make it on every line but more than one may move rapidly through. In the long run, the forecast may be more of a step curve than a gradual smooth uptake. The typical oncology drug has cost nearly a billion dollars to develop in the past, and taken about seven to nine years. Basket studies multiply the potential to find the niche where the molecule has great efficacy—the molecular version of the shotgun approach. While it remains to be seen whether the FDA will be open to seeing these as part of the registration process, they certainly expedite the exploration for the company. Two percent of $10 billion market such as breast cancer would make it worthwhile to bring to market.
Challenge because it strains the organizations as they are built today. We will need commercial organizations to be flexible enough to accommodate changes to their indications and, more important, be willing to spend on various Phase III studies depending on where the product shows efficacy, to really capitalize on the opportunity. Easier said than done—after all, Phase III programs don’t come cheap. It also highlights a bigger challenge: What does it mean when a basket trial shows mixed efficacy results such as this one? Does it have a negative halo on the brand overall? Do payers take heed of this data and restrict usage because of a perceived “limited” efficacy? What does the forecast curve look like in this world? Will you have a peak in six months? The job of insight is about to get a lot harder. Insight needs to shift to a more dynamic mode, able to work with less, in a manner closer to how business development groups usually operate.
Pharmaceutical manufacturers designing their product’s evolution now need to incorporate these studies into the life cycle management plan, and truly be able to assess the value of these. Insight can play a critical role in bringing forth pragmatic skill set building in data and experience. Not a “one study answers all,” but “a basket of research, data and experience” to address business questions.