Genome-targeted therapies have been hailed as a groundbreaking advancement in cancer treatment. But are all of these therapies truly transformative? According to the recent findings published in BMJ, the reality is more nuanced. Only about one-eighth of the genome-based treatments recommended by the National Comprehensive Cancer Network (NCCN) were rated as likely to provide high clinical benefits to patients. This stark contrast has raised concerns about the need for stronger alignment between recommended treatments and actual patient outcomes.
As Dr. Ariadna Tibau, the lead researcher, pointed out, “Our goal was to ensure that treatments recommended for clinical practice not only demonstrate potential on paper but translate into substantial benefits in real-life cancer care.”
A Closer Look at Molecular Target Actionability
The study assessed 411 recommendations involving 74 genome-targeted cancer drugs across 50 different driver alterations. Notably, 84% of these recommendations were based on clinical trials, but many of these trials were early-phase studies. “The majority of the trials we looked at were phase I or phase II, primarily single-arm studies,” said Dr. Thomas J. Hwang, one of the co-authors. “While these trials are crucial for innovation, they do not always offer the robust data necessary to inform clinical practice.”
The researchers used the European Society for Medical Oncology’s (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) to evaluate the clinical impact of these therapies. They found that only 12% of trials showed substantial clinical benefit. This finding is particularly significant because the primary endpoint in most trials was overall response rate rather than patient survival, which is arguably a more meaningful outcome for cancer patients.
Promising But Unproven Treatments
Interestingly, around 33% of the treatments reviewed were classified as offering promising but unproven clinical benefits. “Promising does not always mean proven,” explained Dr. Jerry Avorn. “Patients deserve treatments that are not just hopeful but effective in improving survival and quality of life. Our study shows that many of the treatments currently recommended have not yet crossed that threshold.”
The study highlighted that of the 118 NCCN-endorsed treatments labeled as “preferred,” 53% applied to treatments that offered either high or promising benefits. However, the researchers caution that a promising treatment today could prove to be less effective when more robust data becomes available. “We need more evidence-based recommendations to ensure that cancer patients are receiving the best possible care,” stated Dr. Aaron S. Kesselheim.
Aligning Guidelines with Clinical Reality
This study underscores the importance of aligning clinical practice guidelines with the best available evidence. “We believe that by incorporating more rigorous trial data and focusing on treatments with proven clinical benefit, we can help oncologists make more informed treatment decisions,” said Dr. Tibau. The study calls for a greater emphasis on high-quality evidence when making treatment recommendations.
With advances in molecular tumor characterization and genome-targeted therapies, the potential for improved cancer outcomes remains promising. But as Dr. Hwang emphasized, “Potential must be matched with proven results.”
The researchers conclude that while molecularly targeted therapies hold promise, more stringent measures should be taken to ensure that recommendations reflect therapies backed by strong clinical outcomes.
Citation:
Tibau A, Hwang TJ, Avorn J, Kesselheim AS. Clinical value of guideline recommended molecular targets and genome targeted cancer therapies: cross sectional study. BMJ. 2023;386. doi:10.1136/bmj-2023-079126.
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