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Published on: March 20, 2021
Systematic review of the CUP trials characteristics and perspectives for next-generation studies
Elie Rassy1, Chris Labaki2, Roy Chebel3
1Department of Medical Oncology, Gustave Roussy, Villejuif, France.
Background:
Research on therapeutic strategies for patients with unknown primary cancer (CUP) has been underwhelming. This paper summarized and evaluated the CUP therapeutic research over the previous five years. Based on this evaluation, recommendations for clinical trial designs are made to improve the impact of CUP research on patients.
Methods:
Published and ongoing research were evaluated. PubMed was searched from January 1, 2015, to November 1, 2021. The start date of 2015 was chosen to identify research published after ESMO issued new diagnostic and therapeutic guidelines. The US National Library of Medicine indexed ongoing clinical trials.
Findings:
Of the 244 CUP studies indexed in PubMed, 11.9% were prospective studies, and 4.9% were clinical trials. The review protocol deemed 65 publications eligible for full-text review. Eleven studies evaluating therapeutic regimens were retained. The two prospective studies and non-randomized trials showed promising outcomes for site-specific treatments. Randomized clinical trials were less promising; however, the trials had recruitment challenges resulting in biased accrual and the inability to keep pace with advancing diagnostics and therapeutics. Most of the 35 ongoing studies were phase II single-arm trials assessing immune checkpoint inhibitors (ICI) or site-specific therapies among CUP patients with suspected favorable prognoses.
Conclusion:
Our evaluation suggests two prospective clinical trial designs that addressed recent study design and recruitment challenges. A visionary approach uses a multi-arm, multistage randomized trial to address rapid advancements in diagnosis and therapy. A pragmatic approach utilizes a single-arm trial with historical controls to overcome comparison group and recruitment challenges.
Insights
This study reviews cancer of unknown primary (CUP) research, finding site-specific treatments promising but clinical trials facing challenges. New trial designs are proposed to improve outcomes for CUP patients.
Area of Science:
- Oncology
- Clinical Trial Design
- Cancer Research
Background:
- Therapeutic strategies for cancer of unknown primary (CUP) have yielded underwhelming results.
- A comprehensive evaluation of CUP therapeutic research from the past five years was conducted.
- This analysis aims to inform improved clinical trial designs for better patient impact.
Purpose of the Study:
- To evaluate the landscape of cancer of unknown primary (CUP) therapeutic research over the last five years.
- To identify challenges and successes in existing CUP clinical trial designs.
- To propose novel prospective clinical trial designs for CUP research.
Main Methods:
- Systematic review of published and ongoing CUP research from January 1, 2015, to November 1, 2021.
- Searched PubMed for indexed studies and the US National Library of Medicine for ongoing clinical trials.
- Evaluated 244 CUP studies, with 65 publications undergoing full-text review, retaining 11 studies on therapeutic regimens.
Main Results:
- Only 11.9% of CUP studies were prospective, and 4.9% were clinical trials.
- Prospective and non-randomized trials showed promise for site-specific treatments in CUP.
- Randomized clinical trials faced recruitment challenges, biased accrual, and difficulty keeping pace with advancements; ongoing trials primarily assess immune checkpoint inhibitors or site-specific therapies.
Conclusions:
- Two prospective clinical trial designs are proposed to address design and recruitment challenges in CUP research.
- A visionary approach involves multi-arm, multistage randomized trials for rapid diagnostic and therapeutic advancements.
- A pragmatic approach suggests single-arm trials with historical controls to overcome recruitment and comparison group issues.
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