1. Patients in the MGT group reported a significantly greater progression-free survival than those in the standard platinum-based chemotherapy group.
2. Adverse events were either similar or lower in the MGT group compared to control.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Patients with unfavorable cancer of unknown primary (CUP) have poor outcomes with standard platinum-based chemotherapy, and whether comprehensive genomic profiling (CGP) can improve treatment effectiveness is unclear. This randomized controlled trial aimed to compare the efficacy and safety of CGP-based molecularly targeted therapy (MGT) versus platinum-based chemotherapy in patients who achieved disease control after initial chemotherapy. The primary outcome of this study was progression-free survival, while a key secondary outcome was the safety profile of MGT compared to chemotherapy. According to study results, MGT resulted in a longer median progression-free survival compared to standard chemotherapy. Although this study was well done, it was limited by its open-label design and patient selection biases, which could impact the generalizability of results.
Click to read the study in The Lancet
Relevant Reading: Genome Sequencing as an Alternative to Cytogenetic Analysis in Myeloid Cancers
In-depth [randomized controlled trial]: Between Jul 10, 2018, and Dec 9, 2022, 1505 patients were screened for eligibility across 159 sites in 34 countries outside the USA. Included were patients with unfavorable, non-squamous cancer of unknown primary (CUP) who achieved disease control after three cycles of first-line platinum-based chemotherapy and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Altogether, 436 patients (326 in MGT and 110 in chemotherapy) were included in the final analysis. The primary outcome of progression-free survival was significantly greater in the MGT group compared to the chemotherapy standard (6.1 months vs. 4.4 months, hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.56-0.92, p=0.0079). The secondary outcome of safety showed that adverse event rates were generally similar or lower with MGT than with chemotherapy. Overall, findings from this study suggest that comprehensive genomic profiling followed by MGT offers a survival benefit over standard chemotherapy for patients with unfavorable CUP.
Image: PD
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