Summary of Tweets from Kidney Cancer Medical Symposium

Dear Kidney Cancer Canada subscribers,
Some of you have asked for a written summary of the most recent Kidney Cancer Medical Symposium meeting. This meeting was hosted by the Kidney Cancer Association (KCA) in the U.S.  Thank you to the KCA and specifically U.S. patient advocates Joyce Graff, Mike Lawing, and Katherine Phillion for making me feel welcome. Great meeting!

Disclaimer: all tweets from this meeting were my own personal tweets as a patient advocate. These tweets have not been medically reviewed or endorsed. As always, please consult with your physician about treatment advice.

These updates were sent as a live Twitter feed from my personal account @DebMaskensKCC. If you are new to Twitter, we would also encourage you to follow our official KCC account @KidneyCancer_Ca

Management of Small Renal Masses

  • Dr. David Miller: US data suggest we are moving away from radical nephrectomy. Almost at 50% PN (partial nephrectomise) now. Preserves kidney function.
  • Dr. David Miller: how to explain long-term benefits to patients given possibility of short-term complications
  • Positive margins on partials less than 3% globally. Tony Finelli argues for an individualized approach to each patient
  • Finelli: cites “the healthy user” effect…these  patients will seek out info on partials, avoid smoking, cut back on red meat…
  • Ischemia time can be reduced to zero. Significantly reduces complications. Clamp only on tumor vessels  & keep blood flowing to rest of kidney
  • Dr. Inderbir Gill makes strong argument for robotic surgery at expert centres. Vascular imaging is key.
  • R. Thompson: open partial nephrectomy still the reference standard vs. robotic or lap.
  • Jeffrey Cadeddu on thermal ablation for T1A tumors under 3cm. Efficacy same as partial nephrectomy at 5 yrs
  • Campbell: in some centres, almost everyone gets biopsied now. Active surveillance is an important modality.
  • Dr. Michael Jewett pointing out options to biopsy and active surveillance vs intervention
  • Joyce Graff from VHL Family Alliance pointing out genetic link for 30-year old pt in case study
  • Me: Risk of CKD supports all kidney cancer patients having long-term follow-up plans. Know your creatinine levels.
  • CKD = chronic kidney disease. Living in a world of acronyms here!
  • Campbell: need to separate surgically induced CKD vs CKD from other pre-existing factors. Diabetes, hypertension.
  • Dr. Steven Campbell: are we donating the kidney to the pathologist? The pathologist doesn’t need it all!

Management of Localized and Locally Advanced RCC

  • Case study: role of neoadjuvant therapy to reduce tumor burden. Biopsy, then targeted therapy before surgery
  • Blute: the future of multi-disciplinary care for rcc. Observed improved survival in patients with complete metastasis removal. Requires sub-specialists.
  • Surgery plays a role in every stage of kidney cancer. Requires multi-disciplinary team approach
  • Dr. Michael Blute: role of metastastectomy. Location of mets important — eg, isolated pancreas, adrenal, lymph nodes.
  • Dr. Brad Leibovich on IVC thrombus: imaging must be less than a week old. Performance status best predictor of outcomes.
  • Dr. Jose Karam discussion on comorbidities that affect kidney cancer operability and survival: diabetes, COPD, liver disease, BMI.
  • Dr. Allan Pantuck: role of CAix PET imaging as diagnostic for clear cell rcc. Possibly removes need for biopsy.
  • Biopsies must be done on post-treatment resistant tumors. Patients will start to demand new biopsies vs. Primary. But which to biopsy?
  • Dr. Kim Rathmell: as with breast cancer research on rare subtypes, we need to refocus our efforts on the rare subtypes of rcc. (Parallel to focus on “triple negative breast ca”.)
  • HLRCC info for patients: http://www.hlrccinfo.org/handbook/HLRCC-QUICK-FACTS.pdf …
  • Dr. James Mier on resistance: p53 is activated by Sutent (hypoxia). Sanofi drug MI-319 maintains the p53. Resistance countered.
  • Dr. Pankaj Seth: HLRCC known to metastasize early (2cm). LDH-A dramatically up-regulated. LDH inhibitors to come?
  • Dr. Charles Swanton from UK on drug resistance. Intra- tumor differences in mutations. Primary and met tumors evolve differently.
  • Swanton: are tumors forced down evolutionary routes that are predictable? From trunk to branch, expected mutations?
  • Dr. Aikseeng Ooi on behalf of Dr. Bin Teh: NFR2 activation is at the core of the biology of Papillary mrcc Type 2.
  • Dr. Stephen Boorjian: “need to avoid therapeutic nihilism”. Surgery under-utilization due to lack of awareness. Work to be done!
  • “patients have to undergo the eyeball test” before cyto-reductive nephrectomy.
  • Dr. Bernard Escudier: limit cyto-nephrectomy to good performance patients with large primary tumor and small mets. Not for all metastatic pts.
  • Lung mets: is there a maximum number of lung mets that can be resected? Call of the thoracic surgeons in multi-disc care.
  • Eisen: has there been a change in sites of mets in the era of targeted treatment? More pancreatic, small bowel mets seen?
  • Boorjian: favorable candidates for surgical resection. Solitary site. Lung-only mets. Prolonged (>2 years) from nephrectomy.
  • Lung-only multiple mets patients had significant benefit from resection. Other sites of mets also show benefit
  • Survival benefit of complete surgical resection of all sites of disease. Retrospective data. Selection bias? 50% reduced mortality
  • Surgery most common for lung, bone mets. Strong arguments to remove isolated adrenal, pancreatic mets.
  • Dr. Stephen Boorjian: on surgical removal of mets. 3% CRs on targeted treatment. Potential for curative surgery. Option to delay targeted treatment.
  • Dr. Eric Jonasch: role of neoadjuvant therapy. Safe. Litmus test/predictor of patient performance. Modest, but consistent shrinkage.
  • Dr. Steven Culp: When not to do a cyto-reductive nephrectomy? Higher risk with elderly, non clear cell, or T4 disease
  • Motzer: QoL (Quality of Life) data as secondary endpoint on COMPARZ (1100 pts) tips the scale in favour of pazopanib
  • Brilliant question! “what about the economic toxicities of these drugs?”
  • Dr. Tim Eisen: pazopanib is a standard of care in 1st line, but big things are coming… Possibly tivozanib, Axitinib as 2nd generation drugs
  • Eisen: PISCES showed that only 8% of patients had no preference. Patients with experience with both drugs are in the best position to compare.
  • Eisen: timing of disease and QoL assessments in COMPARZ unfairly favored pazopanib. However, did not affect overall survival data.
  • Motzer: due to geographic distribution of tivozanib study, few patients (only 17%) had access to any 2nd line treatment. Eastern Europe. Sad.
  • Dr. Robert Motzer: arguing for tivozanib as 1st line agent. Strongest PFS in class. OS data at GU ASCO 2013.
  • Porta: biases in PISCES trial? Short period on each drug. Timing of QoL assessment (day 1 to day 28 statistically significant diff).
  • Dr. Camillo Porta: how does recent pazopanib data influence treatment decisions? PISCES showed consistency between patient and physician preference
  • Dr. Brian Rini: advocating for Axitinib as the first-line standard of care for mrcc. titration allows for optimal therapeutic dose
  • Dr. Allison Ackerman: case study w Sutent. Significant toxicity and dose reduction, then Axitinib with few side effects (SEs) and dose titration

Recent Insights into RCC Biology

  • Biopsies must be done on post-treatment resistant tumors. Patients will start to demand new biopsies vs. Primary. But which to biopsy?
  • Dr. Kim Rathmell: as with breast cancer research on rare subtypes, we need to refocus our efforts on the rare subtypes of rcc. (Parallel to focus on “triple negative breast ca”.)
  • HLRCC info for patients: http://www.hlrccinfo.org/handbook/HLRCC-QUICK-FACTS.pdf …
  • Dr. James Mier on resistance: p53 is activated by Sutent (hypoxia). Sanofi drug MI-319 maintains the p53. Resistance countered.
  • Dr. Pankaj Seth: HLRCC known to metastasize early (2cm). LDH-A dramatically up-regulated. LDH inhibitors to come?
  • Dr. Charles Swanton from UK on drug resistance. Intra- tumor differences in mutations. Primary and met tumors evolve differently.
  • Swanton: are tumors forced down evolutionary routes that are predictable? From trunk to branch, expected mutations?
  • Dr. Aikseeng Ooi on behalf of Dr. Bin Teh: NFR2 activation is at the core of the biology of Papillary mrcc Type 2.

Surgery – In the Setting of Metastatic Disease

  • Dr. Stephen Boorjian: “need to avoid therapeutic nihilism”. Surgery under-utilization due to lack of awareness. Work to be done!
  • “patients have to undergo the eyeball test” before cyto-reductive nephrectomy.
  • Dr. Bernard Escudier: limit cyto-nephrectomy to good performance patients with large primary tumor and small mets. Not for all metastatic pts.
  • Lung mets: is there a maximum number of lung mets that can be resected? Call of the thoracic surgeons in multi-disc care.
  • Eisen: has there been a change in sites of mets in the era of targeted treatment? More pancreatic, small bowel mets seen?
  • Boorjian: favorable candidates for surgical resection. Solitary site. Lung-only mets. Prolonged (>2 years) from nephrectomy.
  • Lung-only multiple mets patients had significant benefit from resection. Other sites of mets also show benefit
  • Survival benefit of complete surgical resection of all sites of disease. Retrospective data. Selection bias? 50% reduced mortality
  • Surgery most common for lung, bone mets. Strong arguments to remove isolated adrenal, pancreatic mets.
  • Dr. Stephen Boorjian: on surgical removal of mets. 3% CRs on targeted treatment. Potential for curative surgery. Option to delay targeted treatment.
  • Dr. Eric Jonasch: role of neoadjuvant therapy. Safe. Litmus test/predictor of patient performance. Modest, but consistent shrinkage.
  • Dr. Steven Culp: When not to do a cyto-reductive nephrectomy? Higher risk with elderly, non clear cell, or T4 disease

Options for the Treatment-Naive Patient

  • Motzer: QoL (Quality of Life) data as secondary endpoint on COMPARZ (1100 pts) tips the scale in favour of pazopanib
  • Brilliant question! “what about the economic toxicities of these drugs?”
  • Dr. Tim Eisen: pazopanib is a standard of care in 1st line, but big things are coming… Possibly tivozanib, Axitinib as 2nd generation drugs
  • Eisen: PISCES showed that only 8% of patients had no preference. Patients with experience with both drugs are in the best position to compare.
  • Eisen: timing of disease and QoL assessments in COMPARZ unfairly favored pazopanib. However, did not affect overall survival data.
  • Motzer: due to geographic distribution of tivozanib study, few patients (only 17%) had access to any 2nd line treatment. Eastern Europe. Sad.
  • Dr. Robert Motzer: arguing for tivozanib as 1st line agent. Strongest PFS in class. OS data at GU ASCO 2013.
  • Porta: biases in PISCES trial? Short period on each drug. Timing of QoL assessment (day 1 to day 28 statistically significant diff).
  • Dr. Camillo Porta: how does recent pazopanib data influence treatment decisions? PISCES showed consistency between patient and physician preference
  • Dr. Brian Rini: advocating for axitinib as the first-line standard of care for mrcc. titration allows for optimal therapeutic dose
  • Dr. Allison Ackerman: case study w Sutent. Significant toxicity and dose reduction, then axitinib with few side effects (SEs) and dose titration

Therapy for the VEGF Resistant Patient

  • Dr. William Kaelin: classic drug development model encourages drug companies to kill trials at early phase. Huge expense at phase 3.
  • Kaelin: in single agent use, hit the target as hard as you can.
  • Kaelin: Excuses preventing better trials: …only trial company will let us do..or “our patients won’t let us do that…
  • Kaelin: advocating for smaller randomized phase 2 trials vs expensive phase 3 with marginally separate curves
  • Garcia: case study of 52-yr old woman on Axitinib for 36 months(!) Options for 2nd line post Axitinib not clear.
  • Garcia: arguing that sorafenib (Nexavar) has a place in 2nd line setting. Role of mTOR? Re-biopsy at progression?
  • Dr. Jorge Garcia: how to choose 2nd line therapy. Now have three trials with level one evidence. Select the best treatment up front.
  • Dr. Rupal Bhatt: new targets. Angiopoietin 2 in combination with VEGF inhibitors. Ang2 might be a mechanism of resistance. Trials!
  • Papillary RCC: foretinib study, 74 pts. Tumor shrinkage in 50 out of 68 pts. Germ line mutation = RR 50%.
  • Dr. Tony Choueiri: cMet as target in rcc. Cabozantinib and foretinib. Sporadic clear cell has MET, not just Papillary
  • Need for predictive biomarkers since only a small % of patients likely to derive significant clinical benefit. Trials!
  • Dr. Daniel Cho: beyond VEGF. PI3-Akt inhibitors (mTOR). need to work on issues of resistance, TORC1 and TORC2.
  • Jewett: disparities in access to these drugs around the world. Are we/payers preventing personalization of care?
  • Combinations of therapy to combat resistance? With current drugs, not feasible given increased toxicity without increased efficacy
  • Hutson: uncoupling of PFS as a valid surrogate marker for OS in the second-line setting.
  • Dr. Thomas Hutson: further evaluation is required to determine best 2nd line treatment post-Sutent: Afinitor, Inlyta, (Nexavar).
  • Knox: surprise in INTORSECT study was the overall survival benefit with sorafenib (Nexavar) in 2nd line vs Temsirolimus (Torisel).
  • Knox: everolimus (Afinitor) good option in the 2nd or 3rd line settings. Similar toxicities.
  • Dr. Jennifer Knox (Toronto): primary refractory patients tend to do worse on 2nd line, worse overall survival. Need better options.
  • Larkin: making a strong call for the role of patient advocates in addressing need for biopsy, understanding resistance
  • Larkin: using map of London Underground to illustrate multiple ways to get to destination if one pathway blocked
  • Dr. James Larkin (UK): resistance is inevitable, whether intrinsic or acquired. Can be dynamic and reversible.

Emerging Therapeutic Approaches

  • Dr. Michael Atkins: dosing patients on blood levels might make sense. In absence of test, hypertension might be surrogate marker
  • Atkins: vision – immunotherapy offered first to patients most likely to benefit. Based on tumor markers. Vision? that 2nd line won’t be necessary. How do we get there? Research. Teamwork. Courage. Tenacity.
  • Atkins: Combination therapy with agents that may prevent resistance, eg., Ang2 inhibitors.
  • Atkins: mTOR inhibitors should be limited in rcc to patients whose tumors derive from mTOR pathway? Opinion.
  • New name for BMS936558 = Nivolumab!
  • Dr. Charles Drake: not targeted therapy, but an array of moving targets. Anecdote of pt with 3 doses of PD-1; 4 yrs complete response
  • Drake: potential biomarker of PD-1 to predict response. Trials now testing PD-1 with TKI agents. Other combinations?
  • Dr. David McDermott: parallels to melanoma and newer forms of immune therapy, eg ipilimumab producing durable responses for melanoma.
  • McDermott: pd-1 antibody study still in early trials. No tumor type has more activity with this antibody than kidney cancer. Some CRs
  • McDermott: BMS-936558 drug more active in humans than it is in mice. No maximum dose reached. Durable on drug, some durable off drug
  • Dr. Robert Figlin: recent advances in immunotherapy. IMA901 trial: vaccine with Sutent, phase 3. Accrued in UK, US.
  • Figlin: suggestion that TKIs may work well with immunotherapy agents. Dendritic cell vaccine now being tested with Sutent.

Patient Management Issues

  • Kidney cancer 6th leading cause of cancer death in U.S. One third of patients present with metastasis at diagnosis.
  • Dose reductions in COMPARZ study: 51% of patients on Sutent, 44% of patients on Votrient. Significant percentages need to down-dose.
  • Haas: patient attrition on adjuvant trials has required dose modification. Attrition due to toxicities in otherwise well patients.
  • Dr. Naomi Haas: toxicities of adjuvant therapy? Ejection fracture declines (cardio toxicity) were rare, and reversible.
  • “The impact of targeted therapy is minimal in the African American pop with advanced kidney cancer”. Disparity gap widening.
  • Patients treated at community hospitals in U.S. are 48% less likely to have nephron sparing surgery. Same elsewhere?
  • Income as a determinant: with every $10k increase in income, prevalence of kidney sparing surgery increases by 7%
  • Racial and socioeconomic disparities with nephron-sparing surgeries (NS) in US. Blacks and Hispanics less likely to have NS in U.S.
  • Jewett: quoting KCC survivorship study. Gaps between urologist perception and survivor realities, needs for information on survivorship
  • Jewett: in Canada, we discharge more of our patients to primary care physician than in U.S.
  • Canadian patient Wally Vogel now being profiled for all as new generation patient who has led his own treatment path
  • Dr. Michael Jewett: collaborating to improve survivorship care in kidney cancer. Kidney Cancer Research Network of Canada
  • Third generation drugs such as tivozanib may show better efficacy, improved tolerability. Patient preference will matter in treatment choice
  • Dose escalation of sorafenib back under discussion for improved response. Some studies suggest 74% can double dose.
  • Dr. Elizabeth Heath: importance of dose in rcc therapy. Eg., Sutent dosing from EFFECT trial. Continuous dosing at 37.5 mg
  • Dr. Sumanta Pal: mrcc patients >75 years old are offered fewer lines of therapy; more frequently offered no systemic therapy.
  • Dr. Martin Voss: reporting on exceptional responses to mTOR inhibitors. Mutation of genes TSC1, TSC2, MTOR.  patients on therapy +2yrs

THE END.

Questions welcomed!

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3 thoughts on “Summary of Tweets from Kidney Cancer Medical Symposium

  1. Thanks for putting this together Deb. Would love more details on cabozantinb and when we might see this trial hit Cda.

    The vaccine and sutent one also…..do they need original kidney tumour tissue or can they use a met??? If either has one or the other shown better results?

    Linda.

    1. Thanks for your comments Linda.
      Will definitely share any information about cabozantinib trials and when they might come to Canada. Right now the only studies are Phase 2 (smaller trials) and in the U.S.

      In Canada, we have some Phase 1 trials with the BMS anti-PD1 drug, and a new Phase 2 trial opening next year that will be BMS vs. Afinitor in the 2nd line. Will be opening up in quite a few centres I believe.

      As for the question about vaccine trials and tumour tissue. It’s very interesting because now there is so much evidence that the tumour cells in the mets are different (have evolved) from the primary tumour. So, going with the primary tumour may not be enough. There was some discussion that patients should have a new biopsy after each treatment regimen because of new mutations. Of course, for those of us with multiple sites of disease, that would mean picking a site that was “easy to get to” for a biopsy, but would not necessarily represent the tumour cell make-up in the other mets. They could be different. Makes more sense now why some mets seem to respond and others not so well.

      In short, I was hearing oncologists say “we should re-biospy” a whole lot.
      Also lots of discussion about the role of surgery and how some patients with metastatic disease could be candidates for surgery — especially with few, isolated mets. Not an option for everyone for sure, but there are patients out there on targeted treatments with only a couple of known mets… Might be worthwhile to have that discussion.

      Will keep at this and share what we hear. All the best,
      Deb

      1. Definitely interesting about the vaccine and the source tissue! Regarding surgery I notice (based on reading ACOR and other discussion forums) that in the US it appears that is used much more frequently than up here…..I presumed it was to get rid of the disease, for hopefully once and for all or at least a longer period, but often wondered if it wasn’t also more “cost effective” than long term drug treatment…. I do think, where possible, it makes more sense, especially do too some of the nasty side effects that go along with the treatments.

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