Molecular testing to deliver personalized chemotherapy recommendations: risking over and undertreatment

BMC Medicine

Debate

Vinay Prasad¹  Timothée Olivier² 

[1] Department of Epidemiology and Biostatistics, University of California San Francisco, 550 16th St., 2nd Fl, 94158, San Francisco, CA, USA;Department of Oncology, Geneva University Hospital, 4 Gabrielle-Perret-Gentil Street, 1205, Geneva, Switzerland;Department of Epidemiology and Biostatistics, University of California San Francisco, 550 16th St., 2nd Fl, 94158, San Francisco, CA, USA;

关键词: Adjuvant therapy;    Oncology;    Molecular test;    Gene signature;    ctDNA;    Evidence-based medicine;    Non-inferiority;   

DOI  :  10.1186/s12916-022-02589-6

 received in 2022-08-10, accepted in 2022-09-28,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundIn the adjuvant setting of cancer treatment, de-escalation strategies have the goal of omitting or minimizing treatment in patients, without compromising outcomes. Historically, eligibility for adjuvant treatment solely relied on the patient’s clinical and tumor’s pathological characteristics. At the turn of the century, based on new biological understanding, molecular-based strategies were tested and sometimes implemented.Main bodyHowever, we illustrate how molecularly based de-escalation strategies may paradoxically lead to overtreatment. This may happen when the novel approach is tested in lieu of standard management and may not yield the same results when being implemented in addition to usual practice. In the DYNAMIC trial, adjuvant chemotherapy decision in stage II colon cancer was compared between a circulating tumor DNA (ctDNA)-based approach and the standard care. We show this may result in more patients receiving oxaliplatin-based chemotherapy and may expose a similar proportion of patients to chemotherapy if the novel strategy is implemented in addition to usual practice. The other potential risk is undertreatment. We provide an illustration of early breast cancer, where the decision of adjuvant chemotherapy based on the gene expression signature MammaPrint may lead to inferior outcomes as compared with the clinico-pathologic strategy. This may also happen when non-inferiority designs have large margins. Among solutions, it should be acknowledged that clinico-pathological features, like T4 in colon cancer, may not be abandoned and replaced by novel strategies in real-life practice. Therefore, novel strategies should be tested in addition to standard of care, and not in lieu of. Second, de-escalation trials should focus on the settings where the standard of care has a widespread agreement. This would avoid the risk of testing non-inferiority against an ineffective therapy, which guarantees successes without providing informative data.ConclusionSimply because a molecular test is rational does not mean it can improve patient outcomes. Here, we highlight how molecular test-based strategies may result in either overtreatment or undertreatment. In the rapidly evolving field of medicine, where technological advances may be transformative, our piece highlights scientific pitfalls to be aware of when considering running such trials or before implementing novel strategies in daily practice.

【 授权许可】

CC BY   
© The Author(s) 2022