Cancer remains a major global health challenge, accounting for nearly one in six deaths worldwide. Simultaneously, oncology has entered an era of unprecedented therapeutic innovation, with immune checkpoint inhibitors (ICIs), targeted therapies, and antibody-drug conjugates (ADC) transforming treatment paradigms across multiple tumor types. While these advances have improved outcomes for selected patients, growing concerns have emerged regarding overtreatment, defined as the use of therapies whose harms, costs, or burdens may outweigh their clinical benefits. Increasing reliance on surrogate endpoints, prolonged treatment durations, broad regulatory approvals, and treatment strategies based on highly selected clinical trial populations may expose many patients to unnecessary toxicity and financial hardship. This presentation explores whether current oncology practice is increasingly characterized by \u201ctoo many patients, treated for too long, with too much therapy, too often.\u201d<\/p>\n
Methods:<\/p>\n
A narrative review of pivotal randomized clinical trials, real-world evidence studies, health economic analyses, and regulatory approval data was performed. Key areas examined included patient selection in clinical trials, differences between sponsor-reported and real-world outcomes, the expanding use of immune checkpoint inhibitors, treatment duration, dose optimization, toxicity reporting, and the clinical relevance of surrogate endpoints such as progression-free survival (PFS) and disease-free survival (DFS).<\/p>\n
Results:<\/p>\n
Several patterns suggest overtreatment may be occurring across contemporary oncology practice.<\/p>\n
First,<\/b> many patients receive systemic therapies despite limited likelihood of benefit. In the adjuvant setting, treatments are frequently approved based on improvements in DFS rather than overall survival (OS). For example, therapies such as neratinib and adjuvant immunotherapy have demonstrated modest reductions in recurrence risk while exposing all treated patients to toxicity, inconvenience, and substantial costs. The absence of reliable predictive biomarkers further contributes to overtreatment, particularly in immunotherapy, where clinicians often cannot accurately identify which patients will derive durable benefit and which will not.<\/p>\n<\/li>\n Second,<\/b> treatment durations have expanded considerably. Traditional adjuvant chemotherapy is generally administered for several months, whereas modern immunotherapy and targeted therapies may continue for one to three years. Despite growing evidence that immune activation may persist long after treatment discontinuation, definitive evidence supporting prolonged treatment duration remains limited in many settings. Population-based studies suggest opportunities for treatment de-escalation without compromising outcomes.<\/p>\n<\/li>\n Third,<\/b> many anticancer agents appear to be administered at higher doses and frequencies than necessary for maximal efficacy. Early pharmacodynamic studies of pembrolizumab, nivolumab, and atezolizumab demonstrated target saturation and antitumor activity at substantially lower doses than those ultimately approved. Similarly, studies evaluating low-dose abiraterone administered with food have demonstrated outcomes comparable to standard dosing while significantly reducing costs. These findings raise important questions regarding whether current dosing strategies are optimized for patient benefit or influenced by historical drug development paradigms.<\/p>\n<\/li>\n Fourth,<\/b> reliance on surrogate endpoints may overestimate the value of some therapies. During 2020\u20132022, most oncology drug approvals were based on surrogate outcomes, and only a minority demonstrated improvements in overall survival or quality of life. While PFS and DFS can provide useful information, improvements in radiographic or recurrence-based endpoints do not necessarily translate into longer survival or better patient-reported outcomes.<\/p>\n<\/li>\n Fifth,<\/b> substantial differences exist between sponsor-reported clinical trial results and real-world outcomes. Registration trials typically enroll younger, healthier patients with excellent performance status and limited comorbidities. In contrast, routine oncology practice involves older and more medically complex populations. Real-world studies have consistently reported higher rates of serious adverse events, treatment discontinuation, hospitalizations, corticosteroid use, and chronic toxicities than those observed in pivotal trials. ICIs, antiangiogenic therapies, and targeted agents frequently demonstrate greater toxicity burdens in post-marketing studies than initially reported.<\/p>\n<\/li>\n<\/ul>\n Finally, the economic consequences of overtreatment are considerable. Many novel therapies cost tens or hundreds of thousands of dollars annually, creating significant barriers to access, particularly in low- and middle-income countries. The use of expensive treatments with marginal clinical benefits challenges the sustainability of healthcare systems and may worsen disparities in cancer care.<\/p>\n Conclusions:<\/p>\n Modern oncology has achieved remarkable therapeutic progress; however, more treatment is not always better treatment. The increasing use of therapies with uncertain survival benefit, prolonged treatment durations, non-optimized dosing strategies, and broad application beyond trial populations raises concerns regarding overtreatment. Greater emphasis should be placed on clinically meaningful endpoints, biomarker-guided patient selection, dose optimization, real-world evidence, and shared decision-making. The future of oncology should prioritize value-based, patient-centered care, ensuring that treatment intensity is justified by meaningful improvements in survival, quality of life, and overall patient outcomes rather than by therapeutic escalation alone.<\/p>\n Ivane Kiladze, MD, PhD Medical Oncologists, Head of Oncology Center at CAUCASUS MEDICAL CENTRE\/Ass. Professor at ILIA STATE UNIVERSITY<\/strong><\/span><\/p>\n","protected":false},"excerpt":{"rendered":" Cancer remains a major global health challenge, accounting for nearly one in six deaths worldwide. Simultaneously, oncology has entered an era of unprecedented therapeutic innovation, with immune checkpoint inhibitors (ICIs), targeted therapies, and antibody-drug conjugates (ADC) transforming treatment paradigms across multiple tumor types. While these advances have improved outcomes for selected patients, growing concerns have […]<\/p>\n","protected":false},"author":12,"featured_media":19909,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1673,5891],"tags":[3524,1598,5905,5906],"class_list":["post-19910","post","type-post","status-publish","format-standard","has-post-thumbnail","category-campaigns","category-gimpha","tag-immunotherapy","tag-oncology","tag-overtreatment","tag-ivane-kiladze"],"acf":[],"_links":{"self":[{"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/posts\/19910","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/users\/12"}],"replies":[{"embeddable":true,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/comments?post=19910"}],"version-history":[{"count":2,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/posts\/19910\/revisions"}],"predecessor-version":[{"id":19912,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/posts\/19910\/revisions\/19912"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/media\/19909"}],"wp:attachment":[{"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/media?parent=19910"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/categories?post=19910"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/tags?post=19910"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}