The oncologist
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There is growing interest by patients, policy makers, and clinicians in shared decision making (SDM) as a means to involve patients in health decisions and translate evidence into clinical practice. However, few clinicians feel optimally trained to implement SDM in practice, and many patients report that they are less involved than they desire to be in their cancer care decisions. SDM might help address the wide practice variation reported for many preference-sensitive decisions by incorporating patient preferences into decision discussions. ⋯ Given recent policy movements toward incorporating SDM and translating evidence into routine clinical practice, oncologists are likely to continue expanding their use of SDM and will have to confront the challenges of incorporating SDM into their clinical workflow. More research is needed to explore ways to overcome these challenges such that both quality evidence and patient preferences are appropriately translated and incorporated into oncology care decisions.
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Specific human monoclonal antibodies antagonize cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4 mAbs), a negative regulator of the immune system, inducing unrestrained T-cell activation. In patients with advanced or metastatic melanoma, one of these agents, ipilimumab, produced considerable disease control rates and, for the first time, a clear improvement in overall survival outcomes. However, accumulating clinical experience with anti-CTLA-4 mAbs identified a novel syndrome of autoimmune and autoinflammatory side effects, designated as "immune-related adverse events," including mainly rash, colitis, and hepatitis. ⋯ This condition may be life threatening because of adrenal insufficiency if not promptly recognized, but it may easily be diagnosed and treated if clinically suspected. Hypopituitarism caused by these agents is rarely reversible and prolonged or life-long substitutive hormonal treatment is often required. The precise mechanism of injury to the pituitary triggered by anti-CTLA-4 mAbs is yet to be fully elucidated.
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Lapatinib is a potent reversible and selective inhibitor of the tyrosine kinase domains of epidermal growth factor receptor and human epidermal growth factor receptor (HER)-2 that exerts its action by competitive binding to the intracellular ATP-binding site of the receptor. It is registered for the treatment of advanced or metastatic HER-2+ breast cancer in combination with capecitabine and for hormone receptor-positive breast cancer in combination with an aromatase inhibitor. ⋯ In studies on the efficacy of lapatinib, direct comparisons between lapatinib and trastuzumab are lacking. Results of ongoing randomized phase III studies with lapatinib or trastuzumab in combination with taxanes as first-line agents for metastatic breast cancer as well as in the neoadjuvant and adjuvant settings are awaited.
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Crizotinib, an ALK/MET/ROS1 inhibitor, was approved by the U. S. Food and Drug Administration for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) in August 2011, merely 4 years after the first publication of ALK-rearranged NSCLC. ⋯ Here we summarize the heterogeneity within the ALK- and ROS1-rearranged molecular subtypes of NSCLC. We review the past and future clinical development of crizotinib for ALK-rearranged NSCLC and the diagnostic assays to detect ALK-rearranged NSCLC. We highlight how the success of crizotinib has changed the paradigm of future drug development for targeted therapies by targeting a molecular-defined subtype of NSCLC despite its rarity and affected the practice of personalized medicine in oncology, emphasizing close collaboration between clinical oncologists, pathologists, and translational scientists.
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Triple-negative breast cancer, characterized by tumors that do not express estrogen receptor (ER), progesterone receptor (PR), or HER-2 genes, represents an important clinical challenge because these cancers do not respond to endocrine therapy or other available targeted agents. The metastatic potential in triple-negative breast cancer is similar to that of other breast cancer subtypes, but these tumors are associated with a shorter median time to relapse and death. One important goal is therefore the identification of prognostic factors and markers to reliably select high and low risk subsets of patients with triple-negative disease for different treatment approaches of subtypes with differential responsiveness to specific agents. ⋯ Triple-negative breast cancer is clearly a distinct clinical subtype, from the perspective of both ER and HER-2 expression, but further subclassification is needed. At present, there is not a clear, proven effective single agent that targets a defining vulnerability in triple-negative breast cancer. This article will review the clinical problem of triple-negative disease, potential prognostic factors, demonstrated efficacy of currently available therapeutic options, and new potential therapies.