RE: Detecting Overall Survival Benefit Derived From Survival Postprogression Rather Than Progression-Free Survival

JNCI: Journal of the National Cancer Institute, Jan 2016

Wen-zhuo, He, Liang-ping, Xia

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RE: Detecting Overall Survival Benefit Derived From Survival Postprogression Rather Than Progression-Free Survival

With great interest, we read the brief communication by Morita et al. (1) about overall survival (OS) benefit derived from survival postprogression (SPP) rather than progression-free survival (PFS). The authors performed statistical simulations to explain why experimental treatments could bring survival benefit by prolonging SPP rather than PFS. In other words, the experimental treatment could still exert influence even after having been stopped. We would like to provide clinical interpretations that might account for Prof. Morita’s findings. First, targeted agents may induce clonal evolution among cancer cells. For example, mutated KRAS clones can emerge during cetuximab treatment in colorectal cancer patients who were previously classified as wtKRAS (2). In addition, clonal evolution induced by cetuximab could either be reserved or reversed after cetuximab is stopped. Second, bevacizumab, another commonly used targeted agent, can increase the population of cancer stem cells (3). Third, other angiogenesis inhibitors may also elicit malignant progression by increasing local invasion as well as distant metastasis (4). Fourth, antitumor treatments may not only induce clonal evolution of cancer cells, but also transformation of the host. Chemotherapy-derived inflammatory response, for instance, can promote the function of immunosuppressive myeloid cells (5), thus creating a more favorable microenvironment for the tumor. In conclusion, although experimental treatments were stopped, their effects on reshaping tumor cells and patients were retained. References 1. Morita S Sakamaki K Yin G . Detecting overall survival benefit derived from survival postprogression rather than progression-free survival . J Natl Cancer Inst  . 2015 ; 107 (8) :djv086 doi:10.1093/jnci/djv086. 2. Siravegna G Mussolin B Buscarino M et al.   Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients . Nat Med  . 2015 ; 21 (7) : 795 – 801 . Google Scholar Crossref Search ADS PubMed   3. Conley SJ Gheordunescu E Kakarala P et al.   Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia . Proc Natl Acad Sci U S A  . 2012 ; 109 (8) : 2784 – 2789 . Google Scholar Crossref Search ADS PubMed   4. Paez-Ribes M Allen E Hudock J et al.   Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis . Cancer Cell  . 2009 ; 15 (3) : 220 – 231 . Google Scholar Crossref Search ADS PubMed   5. Takeuchi S Baghdadi M Tsuchikawa T et al.   Chemotherapy-Derived Inflammatory Responses Accelerate the Formation of Immunosuppressive Myeloid Cells in the Tissue Microenvironment of Human Pancreatic Cancer . Cancer Res  . 2015 ; 75 ( 13 ): 2629 – 2640 . Google Scholar Crossref Search ADS PubMed   © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: .


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Wen-zhuo, He, Liang-ping, Xia. RE: Detecting Overall Survival Benefit Derived From Survival Postprogression Rather Than Progression-Free Survival, JNCI: Journal of the National Cancer Institute, 2016, DOI: 10.1093/jnci/djv311