Basket Trials: Review of Current Practice and Innovations for Future Trials

Hobbs, Brian P.; Pestana, Roberto Carmagnani; Zabor, Emily C.; Kaizer, Alexander M.; Hong, David S.

doi:10.1200/jco.21.02285

Cited by 14 publications

(12 citation statements)

References 62 publications

(72 reference statements)

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“…For example, the efficacy of vemurafenib in targeting BRAF V600E mutation in patients with melanoma, [11] was not reproducible in colon cancers [12]. This variability in response has prompted the development and implementation of newer statistical methods for determining efficacy, in an effort to reduce falsepositives because of multiple baskets [13].…”

Section: Discussionmentioning

confidence: 99%

Umbrella review of basket trials testing a drug in tumors with actionable genetic biomarkers

et al. 2023

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Background The utilization of basket trials in oncology has gained popularity because of the drive for precision medicine and the increasing ease of genetically profiling tumors. However, it is unknown if this has translated into patient benefit, either through higher response rates because of precision treatment or because of increasing options for less-common tumor types that are less represented in oncology drug trials. We sought to characterize basket studies for oncology drugs targeting a genetic biomarker, determine the responses for various tumor types and genetic biomarkers, and test for correlation between the number of participants in each tumor basket and the incidence of the respective tumor. Methods We conducted a retrospective cross-sectional review of oncology basket trials on Embase or clinicaltrials.gov with published data. We included studies that reported on oncology drugs that target a genetic biomarker. We examined the response for basket trial participants, stratified by tumor type and genetic biomarker and the correlation between the number of participants in each tumor basket and the incidence of the respective tumor. Results The overall response rate for all 25 included trials was 23%. The response for each genetic biomarker ranged from 0 to 69%, and for half of the genetic biomarkers, the response rate ranged from 0 to 100%, depending on tumor type. There is low correlation between the number of participants in each tumor basket and the incidence of the respective tumor (66.41 + -0.20x, R2 = 0.003, p = 0.75). Conclusion While there has been an increase in the number of published basket trials and individuals included in these trials, the response rate is low, but varies widely, depending on tumor type and genetic biomarker.

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Section: Discussionmentioning

confidence: 99%

Umbrella review of basket trials testing a drug in tumors with actionable genetic biomarkers

et al. 2023

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“…Consequently, most basket trials are prospective phase II clinical trials designed to assess durable and objective therapeutic responses to a targeted treatment across different histologic cancer subtypes ( 9 ). Up to 2019, 49 basket trials were completed and their results were published ( 10 ).…”

Section: Precision Medicine and Tumor-agnostic Approachmentioning

confidence: 99%

Tumor-Type Agnostic, Targeted Therapies: BRAF Inhibitors Join the Group

Vranić

Basu

Hall

et al. 2023

ama

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In the present review, we briefly discuss the breakthrough advances in precision medicine using a tumor-agnostic approach and focus on BRAF treatment modalities, the mechanisms of resistance and the diagnostic approach in cancers with BRAF mutations. Tumor-type agnostic drug therapies work across cancer types and present a significant novel shift in precision cancer medicine. They are the consequence of carefully designed clinical trials that showed the value of tumor biomarkers, not just in diagnosis but in therapy guidance. Six tumor-agnostic drugs (with seven indications) have been approved through October 2022 by FDA. The first tumor-agnostic treatment modality was pembrolizumab for MSI-H/dMMR solid tumors, approved in 2017. This was followed by approvals of larotrectinib and entrectinib for cancers with NTRK fusions without a known acquired resistance mutation. In 2020, pembrolizumab was approved for all TMB-high solid cancers, while a PD-L1 inhibitor dostarlimab-gxly was approved for dMMR solid cancers in 2021. A combination of BRAF/MEK inhibitors (dabrafenib/trametinib) was approved as a tumor-agnostic therapy in June 2022 for all histologic types of solid metastatic cancers harboring BRAFV600E mutations. In September 2022, RET inhibitor selpercatinib was approved for solid cancers with RET gene fusions.Conclusion. Precision cancer medicine has substantially improved cancer diagnostics and treatment. Tissue type-agnostic drug therapies present a novel shift in precision cancer medicine. This approach rapidly expands to provide treatments for patients with different cancers harboring the same molecular alteration.

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“…So ist der Nachweis einer BRAF-p. V600E-Mutation beim kolorektalen Karzinom prädiktiv für das Ansprechen auf eine BRAF-Inhibition (in Kombination mit einer EGFR-Blockade) [3]. Biomarker-stratifizierte Studien können dabei in definierten Tumorentitäten, oder entitätsübergreifend und Histologie-agnostisch, in sogenannten Basket-Trials durchgeführt werden [4]. Ein differentes Ansprechen histologisch unterschiedlicher Tumoren auf eine zielgerichtete Therapie, wie zum Beispiel die eingeschränkte Wirksamkeit einer BRAF-Inhibitor-Monotherapie beim kolorektalen Karzinom, hatte hier bei ersten Basket-Studien zur Vorsicht einer Histologie-unabhängigen Biomarkerdefinition gemahnt [5].…”

Section: Biomarker: Von Prognostisch Zu Prädiktivunclassified