A systematic review of basket and umbrella trials in oncology: the importance of tissue of origin and molecular target

Haslam, Alyson; Olivier, Timothée; Tuia, Jordan; Prasad, Vinay

doi:10.1016/j.ejca.2022.10.027

Cited by 3 publications

(1 citation statement)

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“…Another recent review by Haslam et al. ( 18 ) discussed the importance of tissue origin and molecular target, noting that differences in response rates depended on tumor type. For example, breast and ovarian cancers were likely to have higher response rates than sarcoma or head and neck cancers.…”

Section: Resultsmentioning

confidence: 99%

Basket trials in oncology: a systematic review of practices and methods, comparative analysis of innovative methods, and an appraisal of a missed opportunity

Kasim,

Bean,

Hendriksen

et al. 2023

Front. Oncol.

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BackgroundBasket trials are increasingly used in oncology drug development for early signal detection, accelerated tumor-agnostic approvals, and prioritization of promising tumor types in selected patients with the same mutation or biomarker. Participants are grouped into so-called baskets according to tumor type, allowing investigators to identify tumors with promising responses to treatment for further study. However, it remains a question as to whether and how much the adoption of basket trial designs in oncology have translated into patient benefits, increased pace and scale of clinical development, and de-risking of downstream confirmatory trials.MethodsInnovation in basket trial design and analysis includes methods that borrow information across tumor types to increase the quality of statistical inference within each tumor type. We build on the existing systematic reviews of basket trials in oncology to discuss the current practices and landscape. We conceptually illustrate recent innovative methods for basket trials, with application to actual data from recently completed basket trials. We explore and discuss the extent to which innovative basket trials can be used to de-risk future trials through their ability to aid prioritization of promising tumor types for subsequent clinical development.ResultsWe found increasing adoption of basket trial design in oncology, but largely in the design of single-arm phase II trials with a very low adoption of innovative statistical methods. Furthermore, the current practice of basket trial design, which does not consider its impact on the clinical development plan, may lead to a missed opportunity in improving the probability of success of a future trial. Gating phase II with a phase Ib basket trial reduced the size of phase II trials, and losses in the probability of success as a result of not using innovative methods may not be recoverable by running a larger phase II trial.ConclusionInnovative basket trial methods can reduce the size of early phase clinical trials, with sustained improvement in the probability of success of the clinical development plan. We need to do more as a community to improve the adoption of these methods.

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Section: Resultsmentioning

confidence: 99%

Basket trials in oncology: a systematic review of practices and methods, comparative analysis of innovative methods, and an appraisal of a missed opportunity

Kasim,

Bean,

Hendriksen

et al. 2023

Front. Oncol.

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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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Neoadjuvant therapy in non-small cell lung cancer: basis, promise, and challenges

Kalvapudi,

Vedire,

Yendamuri

et al. 2023

Front. Oncol.

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IntroductionSurvival rates for early-stage non-small cell lung cancer (NSCLC) remain poor despite the decade-long established standard of surgical resection and systemic adjuvant therapy. Realizing this, researchers are exploring novel therapeutic targets and deploying neoadjuvant therapies to predict and improve clinical and pathological outcomes in lung cancer patients. Neoadjuvant therapy is also increasingly being used to downstage disease to allow for resection with a curative intent. In this review, we aim to summarize the current and developing landscape of using neoadjuvant therapy in the management of NSCLC.MethodsThe PubMed.gov and the ClinicalTrials.gov databases were searched on 15 January 2023, to identify published research studies and trials relevant to this review. One hundred and seven published articles and seventeen ongoing clinical trials were selected, and relevant findings and information was reviewed.Results & DiscussionNeoadjuvant therapy, proven through clinical trials and meta-analyses, exhibits safety and efficacy comparable to or sometimes surpassing adjuvant therapy. By attacking micro-metastases early and reducing tumor burden, it allows for effective downstaging of disease, allowing for curative surgical resection attempts. Research into neoadjuvant therapy has necessitated the development of surrogate endpoints such as major pathologic response (MPR) and pathologic complete response (pCR) allowing for shorter duration clinical trials. Novel chemotherapy, immunotherapy, and targeted therapy agents are being tested at a furious rate, paving the way for a future of personalized systemic therapy in NSCLC. However, challenges remain that prevent further mainstream adoption of preoperative (Neoadjuvant) therapy. These include the risk of delaying curative surgical resection in scenarios of adverse events or treatment resistance. Also, the predictive value of surrogate markers of disease cure still needs robust verification. Finally, the body of published data is still limited compared to adjuvant therapy. Addressing these concerns with more large scale randomized controlled trials is needed.

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A systematic review of basket and umbrella trials in oncology: the importance of tissue of origin and molecular target

Cited by 3 publications

References 5 publications

Basket trials in oncology: a systematic review of practices and methods, comparative analysis of innovative methods, and an appraisal of a missed opportunity

Basket trials in oncology: a systematic review of practices and methods, comparative analysis of innovative methods, and an appraisal of a missed opportunity

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

Neoadjuvant therapy in non-small cell lung cancer: basis, promise, and challenges

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