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Presentation Notes An Overview of the Proceedings Twelfth International Kidney Cancer Symposium John C. Cheville, M.D. reports on a new RCC subtype during the Symposium Clearcell papillary tubulopapillary RCC is a distinct entity different from CC and papillary types. It tends to be low grade, not very aggressive, rarely metastasizes, and may become the 3rd most common subtype as it is more widely recognized and listed in pathological reports. DESPITE THE AMAZING PROGRESS OF THE LAST DECADE T

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 2 Dear Readers I am privileged to submit this patient summary of the 12th Annual International Kidney Cancer Symposium for your consideration. Hosted by the Kidney Cancer Association, this twoday meeting is in the words of Dr. Nicholas Vogelzang invigorating in ways that are impossible to define. The symposium focuses on kidney cancer, and draws together a slate of presentations by knowledgeable experts of interest to clinician

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 3 Table Of Contents 4 Update on Active Surveillance Michael A.S. Jewett, M.D. 6 Recognizing Morton A. Bosniak, M.D. 7 Debate RFAMicrowave is Best for Ablation Patients Fred T. Lee, M.D. 8 Debate CRYO IS BEST for Ablation PatientsThomas D. Atwell, M.D. 9 PRO Renal Mass Biopsy Alexander Kutikov, M.D. 10 CON Should Renal Mass Biopsy be Performed Routinely Brian Lane, M.D., Ph.D. 11 Role of Fluorescence Imaging During Partial Nephr

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 4 Update on Active Surveillance Dr. Michael Jewett gave his assessment of where he felt the medical community is today in the practice of active surveillance AS of Small Renal Masses SRM for kidney cancer. He defined a small renal mass as a clinical entity that now leads to over half of the new diagnosis of kidney cancer. These SRMs are typically nonsymptomatic, less than 4 cm in size, and are often found incidentally when an M

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 5 including pathologists, imagers, and others to interpret the collected tissue. Biopsies are usually performed using an 18 gauge core biopsy needle guided by CT or ultrasound imaging according to Dr. Jewett at least 80 of these biopsies yield what could be classified as diagnostic quality samples. Inconclusive biopsies are now beginning to be followed up with what is termed a B2 biopsy a repeat of the first biopsy which also c

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 6 Our triggers for treatment though are poorly understood at this time we tend to use size and kinetics. Kinetics is the estimated growth potential of the mass based on evidence from other instances of metastases andor growth patterns of similar renal masses. An SRM that matches others that have a rapid initial growth pattern will be more likely to receive treatment than a mass that matches indolent profiles. We do not have a g

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 7 A Comparison of Ablation Therapies CA, RFA MW Discussed RFAMicrowave is Best for Ablation Patients Fred T. Lee, M.D. University of Wisconsin Hospital Madison, WI In terms of Microwave and RF ablation, Microwave is RFs big, tough, older brother. The key with heatbased ablation is getting the tissue temperature to 60C at which time the tissue dies very rapidly within seconds. In his presentation on the case for heatbased abl

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 8 With cyroablation the visible ice ball that is observed via imaging during treatment does not always equal the kill area which is sometimes as much as 1 cm smaller. Some cells are more resistant to freezing than others Summary Stateoftheart ablation works for small RCC CA RF essentially equal for tumors 3 cm Think of MW as an improved RF modality If cost is an issue to you, think heat Cryo has more data, its just older

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 9 Dr. Atwell echoed the earlier comments on Dr. Lee that RF, MW, and cyroablation are all capable and pretty much equal in efficiency in the treatment of small renal masses it is the utilization of the best skill sets and tools that are available at the treatment facility that will optimize the best outcomes of the patient. Where heatbased and cyro therapies are both available with equally skilled clinicians Atwell would be inc

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 10 inability to distinguish between aggressive and more indolent tumors. Currently the accuracy level is below 85 in some situations the accuracy is as low as 62. He did report on one study where the accuracy was listed at 91 but maintained that studies from other centers on similar procedures would be needed to validate these findings. In summary Dr. Kutikov maintained that while renal biopsy presently has limited clinical val

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 11 Dr. Lane cited the three main concerns for not performing a biopsy were the following Needle tracking this is an unfounded concern which was examined here earlier by Dr. Kutikov additionally the April 2013 AUA guidelines place the risk at less than 0.01. Undesirable rates of finding indeterminate or inaccurate diagnosis. The assumption that since 80 of SRMs are cancerous anyway it probably will not change what is done so

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 12 Michael D. Stifelman, M.D. NYU Langone Medical Center New York, NY We may potentially be improving the postoperative outcomes by minimizing damage to the normal part of the kidney while excising the tumor itself Dr. Michael Stifelman presented information on the use of near infrared fluorescence imaging during robotic renal surgery. This technology shows initial promise in helping to reduce the need for clamping off blood

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 13 Summary and Case Presentations Kidney Cancer and Risk We have a cancer problem in this country... We are better at finding these cancers early than we are fixing these cancers early. Our diagnoses of kidney cancer are increasing and our deaths remain about the same. Our technology of finding the cancer has improved but our understanding of the biology of cancer, our understanding of how to fix cancer has not improved as much

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 14 In medicine we have to educate for avoidable risks, communicate absolute risks, accept calculated risks, and study unexpected risks. As humans we try to manage risk all the time because we try to predict the future. We do so with real estate, stocks, weather etc. In the field of medicine we need to be working at managing what is probable not what is possible. When flying a plane crash is possible, but not probable that is wh

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 15 Chronic Kidney Disease and Competing Comorbidities In the Management of Localized RCC Patients with kidney cancer can die from kidney cancer, or they can die of other causes. Death from kidney cancer is determined by tumor characteristics i.e. tumor size, stage and grade whereas death from other causes is determined by patient age and other medical problems e.g. heart disease. There is an emerging link between medical kidney

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 16 Nephrectomy for Larger Renal Masses There is essentially not a great deal of difference in partial and radical nephrectomies for tumor masses in the 47 cm range. Complication rates are higher in larger tumors with partial nephrectomies. The two illustrations below depict a very challenging situation where a partial nephrectomy was necessary. This is a 46yearold male presenting with a 29 cm left renal mass he had donated his

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 17 Management of IVC Thrombus An IVC thrombus may or may not block the flow of blood while most patients present with a constellation of problems, some are asymptomatic. Sometimes the thrombus is mobile which makes surgery a lot easier and sometimes it invades into the actual wall of the inferior vena cava and patients may require resection and grafting E. Jason Abel, M.D. University of Wisconsin Hospital Madison, WI

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 18 Role of Lymph Node Dissection Vitaly Margulis, M.D. University of Texas Southwestern Medical Center Dallas, TX In a population of patients with clinically localized kidney cancer I think routine lymph node dissection is not necessary

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 19 Followup of Patients After Surgical Treatment No single followup plan is appropriate for all patients therefore, individual followup plans should be developed that take into account the size, stage and grade to estimate a relative risk of relapse. NCCN guidelines, Version 1.2013 Kidney Cancer Viraj Master, M.D., Ph.D., FACS Emory Winship Cancer Institute Emory University, Atlanta, GA ... As for as pet scans, much like the

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 20 Summary and Case Presentation for Management of LocalizedLocally Advanced RCC Dr. Campbell summarized the segments on localized RCC, addressing some of the major issues frequently encountered with this condition and commented on the quality and availability of data for these items. Active Surveillance The AUA will be establishing new guidelines for active surveillance in the next few years. The present role of AS is a reason

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 21 Christopher G. Wood, MD, Honored By Kidney Cancer Association Delivers Novick Memorial Lecture at International Kidney Cancer Symposium Chicago, IL PRWEB October 25, 2013 Christopher G. Wood, M.D., F.A.C.S., was honored at the 12th International Kidney Cancer Symposium, held in Chicago, for his careerlong commitment to advancing kidney cancer research. On Friday, October 25, he delivered the Andrew C. Novick Memorial Lectur

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 22 Emerging Aspects in the Biology of RCC Translational Biology of RCC Whats Next James Brugarolas, M.D., Ph.D. University of Texas Southwestern Medical Center, Dallas, TX Our therapeutic advances are going to come through a better understanding of the molecular genetics and biology of renal cancer. Knowing the genes is not enough we need to understand the pathways knowing the pathways is not enough we need to know the protei

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 23 Understand and exploit mutation heterogeneity. The study by Gerlinger at bottom of page can be good news and bad news. The good news is it can help us identify the mutations that we should be focusing on. Isolate biologically distinct entities in renal cancer develop a molecularlybased classification. It is important to isolate biologically distinct entities in kidney cancer. We need to develop a classification system that

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 24 Recognizing W. Marston Linehan, M.D. Urologic Oncology Branch Chief Center for Cancer Research National Cancer Institute Bethesda, MD Kidney cancer is not a single disease. Its made up of a number of different types of cancer, which happen to occur in the kidney. Each of these cancers has a different histologic type, each has a different clinical course, each responds differently to therapy and each is caused by a different

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 25 AUC stands for area under the curve imagine the typical bell curve with efficacy on the left and toxicity on the right. The area under the curve is the fine balance between efficacy and toxicity for patients. Things that interfere with the AUC are compliance in taking the medication which in cancer patients is fairly good according to studies, the dose and schedule in which it is administered, the amount of absorption which

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 26 CardioOncology in RCC An Update Juan Carlos Plana, M.D. Taussig Cancer Institute Glickman Urological and Kidney Institute Cleveland, OH Many patients who are on sunitinib demonstrate high blood pressure. This includes patients who have previously had no heart problems or coronary artery disease CAD but when tested after several cycles of therapy exhibit conditions similar to CAD. Mouse models were used in an effort to replic

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 27 Rana McKay, MD DanaFarber Cancer Institute Boston, MA Impact of Bone Metastases BM and Bisphosphonate use in Patients with Metastatic Renal Cell Carcinoma mRCC Treated with Targeted Therapy Results from a Pooled Clinical Trials Database Dr. McKay presented the results of a pooled retrospective analysis of 2479 patients with metastatic renal cell carcinoma that were treated on phase II and phase III trials sponsored by Pfiz

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 28 At the end of Dr. McKays presentation she listed the following conclusions The presence of bone metastases is an adverse risk factor for survival in patients with mRCC Although underutilized, bisphosphonate therapy did not impact the rate of SREs or survival Bisphosphonate therapy BSP was associated with increased rates of hypocalcemia, renal insufficiency, and Osteonecrosis of the jaw ONJ A definition for SKELETALRELATED EV

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 29 Dr. Leibovich presented several cases for the panel and the audience to consider. While the following case and its outcome demonstrates a dramatic response to targeted therapy and then surgery it does not reflect typical results. 67 yo male with history of 3.5 cm AAA Abdominal Aortic Aneurysm arterial fibrilation on coumadin, current smoker June 2009 imaging to follow up on AAA... which has been neglected for awhile AAA has

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 30 Debate Cytoreductive Nephrectomy First This is not a blackandwhite issue but a continuum denying everyone cytoreductive nephrectomy up front in favor of targetedtherapy may not be a good thing. Gennady Bratslavsky, M.D. SUNY Upstate Medical University Syracuse, NY Dr. Bratslavsky pointed out that prior to the targeted therapy era few patients that were eligible for surgery for a kidney tumor were placed on IL2 or interfero

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 31 In the preTKI era before December, 2005 when there were few effective treatment options, nephrectomy was the standard of care for metastatic patients. The median survival in those days was 12 months or so, today it is around 30 months. Today some patients are being offered therapy instead of surgery as first option of treatment. While data suggest that nephrectomy patients still do better, it may be a bit more complicated wh

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 32 Lymph Node Dissection LND During Cytoreductive Nephrectomy CR In his opening remarks Dr. LaRochelle stated that this is a topic with limited amount of data and was not a discussion of lymphadenectomy for someone who has bulky nodal disease in the absence of systemic or distant site metastasis the discussion would cover only the lymph node positive or negative disease in the setting of distant sites of metastases. An explanat

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 33 Reasons not to do LND or CN in cNM clinically node positive with metastatic disease NM RCC has very poor prognosis Are these patients benefitting from CN Patient selection for CN Culp et al, Cancer 2010 Identified 7 preoperative risk factors that portend shorter survival after CN 4 risk factors do not appear to benefit med survival 8.5 mos albumin LDH cT3 or cT4 Symptomatic met Liver mets Retroperitoneal LAD lymphadenopat

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 34 Role of Metastasectomy Metastatic RCCEpidemiology 65,150 patients will be diagnosed with renal tumors in 2013 in the US 90 RCC 30 are stage IV at diagnosis synchronous 3040 stage IIII at diagnosis mets later metachronous Metastatic RCCChallenges Minority respond to cytokine therapy Rare complete responses with targeted therapy Not responsive to most chemotherapy Not responsive to radiation therapy MetastasectomySurvival bene

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 35 Retroperitoneum most common recurrent sites here are adrenal gland, fossia, lymph nodes 54 patients 5 Predictors of poor outcome at time of local recurrence Positive surgical margin Recurrent tumor size 5cm Sarcomatoid features Abnormal alkaline phosphatase Increased lactate dehydrogenase Cancer specific survival Median Overall 61 months 0 risk factor 111 months 1 risk factor 40 months 2 risk factors 8 months Liver 2yea

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 36 RCC The Role of the Pathologist Subtypes of RCC Clear cell renal cell carcinoma Papillary renal cell carcinoma Clear cell papillary tubulopapillary renal cell carcinoma Chromophobe renal cell carcinoma Collecting duct carcinoma Translocation associated RCC Mucinous tubular and spindle cell RCC Tubulocystic RCC John C. Cheville, M.D. Mayo Clinic Rochester, MN The current method of classification of RCC was established in 19

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 37 30 of pathologists did not mention necrosis in their pathology reports and yet it is an important factor to report. Necrosis rarely appears in grade 2 tumors, and only about 20 of grade 3. Tumors with sarcomatoid features do worse than those with no sarcomatoid. Historically, pathologists have focused on the peripheral perinephric fat, not the renal sinus fat where venous and lymphatic drainage occurs Comments from Ken, Spo

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 38 A Joint Session on Immunotherapy James H. Finke, Ph.D. Department of Immunology Cleveland Clinic Taussig Cancer Institute Cleveland, OH If we can understand more about the tumor microenvironment we might be able to come up with additional targets for immunotherapy Introduction by Dr. James H. Finke The Society for Immunotherapy of Cancer is a membershipbased network of over 800 members from 35 countries of clinical and basi

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 39 Tcell responders are powerful If you get a virus infection Tcells will mount a response and the next time a virus comes into your body they will mount a response even before you develop symptoms T cells are capable of recognizing the antigens capable of producing memory cells capable of producing a response to another antigen it can recognize millions of antigens So why are they not recognizing the tumor antigens Cancers

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 40 We need presurgical tissue to understand what Tcells and other cells are doing in the tumor microenvironment, then later collected tissue to see how the therapy affects them and perhaps what possible therapy combinations we can try. Tumor tissue also guides us in biomarker discovery. The metastatic disease has gone away, not only in visceral soft tissues but also in a bony met that was resolved with PD1. Sequential biopsies

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 41 Tumor cells arent stupid they can evolve away from the specific antigen being targeted by the Tcell response so the broader the repertoire of antigens targeted the greater the chance of therapeutic efficiency RCC CC An Immunogenic Cancer Rare spontaneous regressions of RCC observed in association with inflammatory cell infiltrates andor enhanced peripheral Tcell function. Progressor RCC with accumulated defects in antigen

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 42 PD1 Pathway Immunotherapy If PD1 pathway immunotherapy makes it to the clinic there will be a relearning process by physicians to be more aware of the side effects autoimmunity of an immunotherapy drug and of being able to use these drugs for most effectiveness and quality of life. Gordon Freeman, Ph.D. DanaFarber Cancer Institute Harvard Medical School Boston, MA Immunology has offered hope for curing cancer for 100 years

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 43 PD1 pathway immunotherapy 2050 response rate in clinical trials Topalian et al., NEJM 3662443 2012 Effective in multiple tumor types melanoma, renal, lung, others Durable responses, some that last years Well tolerated no nausea, no hair loss. This is not chemotherapy Good safety profile PD1PD1 Ligand molecule pathway mediates Tcell exhaustion in Chronic Viral Infection TumorInfiltrating T cells TIL behave like exhauste

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 44 Update Health Outcome Research in Advanced RCC Daniel Heng, M.D., MPH, FRCPC University of Calgary Tom Baker Cancer Center Calgary, Canada An important question is WHAT CAN OUTCOME RESEARCH DO Utilizing outcomes databases we can capture the real world experience of targeted therapy identify trends in practice develop prognostic factors and can better be able to answer clinical questions that create hypothesis generation ahe

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 45 The International mRCC Database Consortium Currently includes 3300 patients from 23 institutions Intl mRCC Database Consortium Prognostic Factors KPS 80 Karnofsky Performance Scale Dx to Tx Interval 1yr Anemia Hypercalcemia abnormally high level of calcium in the blood Neutrophilia high white blood cell count Thrombocytosis high blood platelet count If patient has 0 factors Favorable Prognosis If patient has 12 factors

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 46 Implications we retrospectively looked at the response rate of patients that were treated with two VEGF inhibitors, a first line and then a second line. Even if the best response with first line was progressive disease there was still an 11 chance of a response to second line therapy and another 34 of patients had stable disease. Choice of secondline therapy should not be dependent on response to firstline therapy E.g. if po

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 47 Karnofsky Performance Status National Cancer Institute At the Eastern Cooperative Oncology Group we have some really large clinical data sets and we have a very large tissue repository. I think there are some exciting new agents out there for example the chromatin modulating genes. There may be some glimmers of ways that we can refine risk in renal cell and direct that forward in new neoadjuvant trials. Naomi B. Haas, M.D

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 48 Newer TKI Agents in the Front Line Setting Pro C. Lance Cowey, M.D. Texas OncologyBaylor Charles A. Sammons Cancer Center Dallas, TX Key Questions Conclusions Are the newer TKIs more appropriate for future combination therapies Yes. Tolerability in combination studies with newer, selective TKIs is improved over older TKI drugs. If we are reaching an efficacy ceiling with single agent targeted therapies, then we need our bes

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 49 Newer TKI Agents in the Front Line Setting Con Treatment Algorithm for New Clear Cell RCC Patient Assess Urgency of Treatment Remember, RCC can be very indolent Assess Eligibility for High Dose IL2 Assess Eligibility for Immunotherapy Clinical Trial Assess Eligibility for other Clinical Trial Assess Disease Status Asymptomatic vs Symptomatic Extensive vs Limited Oligometastasis consider surgery a few metastatic spots that a

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 50 HighDose IL2 Therapy FDA Approval 1992 Response Durations of 255 pts in 2002 15 response rate with durable responses in a small percentage of patients Med Response Duration all partial response patients avg 50 months duration not reached for CRs Drawbacks Significant toxicity and cost Application limited to selected patients treated at selected centers Clinical Trials of Immunotherapy Checkpoint inhibitors To me most of th

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 51 Patient Selection for Upfront mTOR Inhibition Biologic Rationale Rationale for mTOR as a Therapeutic Target PI3KAktmTOR signaling pathway is dysregulated in many cancers including RCC Activation of this pathway has been suggested to correlate with aggressive behavior and poor prognosis in RCC tumors Although mechanism of antitumor activity is not completely clear clinical efficacy of these agents is well established Temsirol

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 52 When you go to work and think about kidney cancer keep your passion Dr. Schonfeld was a very passionate man and I think his passion has driven this organization the Kidney Cancer Association to where it is today and going forward. I do believe that we are at a bit of a plateau. While it is pretty amazing to look at 2013 as compared to 1980, we are still not curing people and I still think that the drive for most of what we d

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 53 In the 1980s there was a shift from cytotoxic chemotherapy to immunebased treatments. We saw some complete responses and partial responses lasting longer than a year neither of which had been seen with chemotherapy. We have not done a very good job in kidney cancer in combining agents is it the disease, is it the agent, is it the novelty Were not exactly sure but there is some commonality across the decades where combining

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 54 pathway in subsequent therapies. I know we have seen different things in this regard, but I dont think that we have asked the question properly just yet. I do think there are a group of patients, perhaps 15 to 20 that march right through the current TKI and mTOR inhibitors its a different disease subtype they are dealing with. I think there is a group of patients that have a spectacular response to the VEGF receptor TKIs o

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 55 One of the lessons I learned in the last seven years is it is sometimes very good to change institutions and you can say to yourself why is that Everybody does best by spending 100 years at the same institution Im one of the reasons you can change institutions is that you can discover science that might not be relative to what they were thinking that you might then think about or get them to think about. In his summary Dr. F

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 56 Dr. Figlin has authored over 300 peerreviewed articles, more than 60 book chapters, and has published many books W. Kimryn Rathmell, M.D., Ph.D. on kidney cancer. He University of North Carolina Linberger Comprehensive Cancer Center serves as the Editor of Chapel Hill, NC the Kidney Cancer Member Scientific Program Committee Journal his studies have 2013 Kidney Cancer Symposium appeared in the Journal of Clinical Oncology, t

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 57 Existing Clinical Data of SecondLine and Greater Therapy in Advanced RCC An area of kidney cancer which has seen the most rapid growth of new data over the past 16 months is in the second line and greater refractory population which is resistant or nonresponsive to a treatment. As a reminder overall survival is the key. It seems like we are accomplishing that with sequential therapy. We must think beyond firstline therapy wh

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 58 Trial data for everolimus indicated good application for second line therapy however consequent trials and indications are that it may be better used as third line and later therapy. The everolimus trial had significant numbers of patients enrolled who were in third line and beyond. Axitinib was indicated for second line it is a potent TKI. It is hoped it would provide as great an efficacy with lower toxicity and have a sign

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 59 Sunitinib Rechallenge The response to a sunitinib rechallenge may depend on the time interval between usasge of the drug. The median PFS of initial treatment with sunitinib was 13.7 months compared to 7.2 months for rechallenge p0.04 Patients with a 6 month duration between sunitinib treatments n14 had a longer PFS than patients who were rechallenged within 6 months n9 median PFS 16.5 vs. 6.0 months p0.03 There was no signif

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 60 Update in the Biology of Resistance Disease Our challenge is that when we give a drug to a patient there is sometimes no response at all for others there is a response, but usually over time resistance develops the drug is no longer as effective in controlling disease. If there is no shrinkage with TKI the tumor is resistant to that drug and there seems to be some correlation about how the tumor has developed. In the slide

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 61 In instances where there has been a response and then resistance develops some of the resistance mechanisms may be transient. By stopping the drug when resistance is encountered the resistance mechanism is often diminished which allows for a response if treatment is restarted later. Clinical trials have been largely responsible for important advances in the treatment of kidney cancer in recent years. The key to their success

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 62 We have a lot of choices, but there are also limitations to all of our treatments what we really want are treatments that produce durable responses in the majority of patients. Right now we have IL2 with durable response in very limited patients VEGF inhibitors that are largely palliative we want to be able to give those that will have the best results for each patient. Key Issues Optimizing VEGF Inhibitors The Role of MT

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 63 PD1 Pathway Blockade Key Translational Questions Is PDL1 expression Influenced by prior systemic therapy Predictive of benefit for that other therapy Is some other biomarker better Is PD1 blockade better applied in the treatment nave or resistant setting What are the mechanisms of resistance to PD1PDL1 pathway blockade Are they key to rationale combination therapy Particularly relevant if other immunoregulatory pathwa

Twelfth Annual International Kidney Cancer Symposium 2013 Lawing 64 Commentary For What Its Worth THE HAUNTING CHALLENGE OF EUGENES BLACK BAG FOR ALL OF US Michael B. Lawing Patient Advocate KCA Board Member It is indeed quite a challenge to summarize the proceedings of the 12th Annual International Kidney Cancer Symposium in such a way that is both relevant and meaningful to survivors, caregivers, and others who are laypersons with little medical background. Dr. Eugene Schonfelds statemen

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