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Journal of Clinical Oncology, Vol 25, No 29 (October 10), 2007: pp. 4691-4692 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.12.7613
Targeted Therapies: Cui Prodest?Department of Medical Oncology, San Paolo Hospital, Milan, Italy To the Editor: Hoff and Ellis in their Editorial1 rationally argue on the actual goal of clinical investigation on targeted therapies in oncology. In this era of fast developing new molecules, monoclonal antibodies (MoABs) targeting either the vascular endothelial growth factor or epidermal growth factor receptor are widely studied and tested. We agree with the authors that results of recent trials in metastatic colorectal cancer and pancreatic cancer can be viewed as quite disappointing considering that overall survival (OS) is not significantly increased. Even improvement in progression-free survival can be considered not so impressive, both from the patient's and doctor's points of view. In the trial reported by Van Cutsem et al,2 the gain in median progression-free survival is 5 days with panitumumab, and that is the problem. How can we really believe that 5 days are meaningful in the battle against cancer? Why should we convince a patient to participate in a clinical trial on molecular-targeted agents with such a dismal perspective? And what about OS, which seems to be more likely a chimerical dream than a concrete option? In the study of the National Cancer Institute of Canada,3 a biologic agent like erlotinib increases OS by 0.33 months when combined with gemcitabine in advanced pancreatic cancer. It means that we offer to this severely ill population a gain of 10 days. When designing a trial intended to demonstrate the effectiveness of an innovative therapy, researchers and clinicians do harbor a cautious sense of reality; nonetheless the hope that something is changing and that future results could exceed the older ones is always inside every investigator. The authors ask, for whom are we doing these trials? We know that immunohistochemical expression of epidermal growth factor receptor is not a predictive factor for efficacy of MoABs,4 and the presence of a receptor is probably less important than the activation status of that receptor.5 We know that various mechanisms of resistance can decrease the efficacy of biologic treatments,6 and we are still searching for those that could predict response in a specific patient. We also know how crucial the approval strategies for the pharmaceutical companies are. Yet, these trials are planned and performed for each patient with metastatic cancer who asks for not only a cure but who lavish on modern oncology a great hope for his/her own life and everybody's life. Indeed, we are still far away from a lot of answers, but we are conscious to erode day by day the big stone of ignorance. Five days today might become 50 or 500 days next year. It might sound unlikely, but never as in the last few years has the speed of science been so great. Even if the difficulty to understand and block all the pathways involved in carcinogenesis is evident, nonetheless, it is now clear that the combination of chemotherapy and targeted therapy will improve results without adding severe toxicity. This is already a great result. Trials designed to evaluate the combination of diverse MoABs without the use of chemotherapeutic agents are ongoing. This will be another step on the road to hit the target. Let's wait trustfully on the events approaching, without forgetting the high burden to society in terms of economic cost7,8 whenever new agents are combined to improve clinical results. New drugs should not be available only to people who can afford this cost; rather, every effort should be undertaken to share knowledge and make treatment sustainable at any latitude. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Hoff PM, Ellis LM: Targeted therapy trials: Approval strategies, target validation, or helping patients? J Clin Oncol 25:1639-1641, 2007 2. Van Cutsem E, Peeters M, Siena S, et al: Open-label, randomized, phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25:1658-1664, 2007 3. Moore MJ, Goldstein G, Hamm J, et al: Erlotitinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: A phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25:1960-1966, 2007 4. Saltz LB, Meropol NJ, Loehrer PJ Sr, et al: Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22:1201-1208, 2004 5. Camp ER, Summy J, Bauer TW, et al: Molecular mechanisms of resistance to therapies targeting the epidermal growth factor receptor. Clin Cancer Res 11:397-405, 2005 6. Brixner DI, Bull SA: The challenge of integrating monoclonal antibodies into the current healthcare system. Am J Manag Care 3:903-911, 1997[Medline] 7. Baselga J, Arteaga CL: Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol 23:2445-2459, 2005 8. Clegg A, Scott DA, Sidhu M, et al: A rapid and systematic review of the clinical effectiveness and cost-effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small-cell lung cancer. Health Technol Assess 5:1-195, 2001[Medline]
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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