Brian Rini, MD
@brian_rini
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Joined June 2014
The RCC biomarker field is gathering steam. Stellar review of the field by VUMC Fellow Matthew Tucker here:
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Updated table of the latest data for initial IO-based therapy in IMDC Int/Poor mRCC. See thread for discussion of imperfections and thoughts.
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Updated IO combo table after #ASCO2023 IO/TKI presentations. VEGF tx provides early disease control while Ipi provides durability. We need a way to harness the benefits of both approaches. @montypal @DrChoueiri @tompowles1 @motzermd @HHammersMD
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An updated table of the front-line IO combination RCC studies that have shown an OS advantage.
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New table of IO doublets in sarcomatoid RCC:. 1. Central path review done for ipi/nivo while other datasets relied on local path report.2. IO/VEGF with very short f/u and thus wide CIs.3. Ipi/nivo notable for high CR rate and high landmarks with long f/u.4. No detailed CLEAR data
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Why does PD-1-based therapy have superior outcomes in RCC? To me the clinical data are clear. All PD-1-based trials positive for OS, all PD-L1-based trials are negative. Summary data for IO/TKI trials here:
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Nick was an inspiration to me since I was a Medicine Resident on his service in 1998. He is the reason I became a GU Oncologist. He made me a better doctor and a better person. Calling him a legend doesn't seem nearly enough. Rest in peace my friend.
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Updated table of IO doublets in mRCC after #ASCOGU22: .1. Consistent OS benefit; medians immature for IO/TKIs.2. IO/TKIs with more tumor shrinkage; higher ORR, longer PFS and less early PD.3. Ipi/Nivo has the most durable benefit at 5 years -IO/TKI data immature
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New table highlighting results in IMDC favorable risk RCC across IO-based doublets and nivo/pembro monotx trials. Major caveats about small subsets and differing follow-up, but interesting observations emerge. Thanks to @DrChoueiri and Mike Atkins for help assembling data.
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Updated table of IO combos (ITT population) in front line mRCC after #ASCOGU24. Has anything changed for you based on these data?
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Updated table of OS-improving IO-based combinations in mRCC. Some details pending #ASCOGU presentations and publications. Much to discuss. #uromigospodcasts
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Updated table post ASCO 2021. Best to focus on building on these combos to cure more patients than on comparing across regimens.
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Updated summary after #ESMO21. Thanks to @ERPlimackMD for help. Not well-captured are some of the durable benefits of Ipi/nivo. Note median OS nearing 5 years! Awaiting mature data for IO/TKI regimens. Let's move to biomarker-based designs and not argue regimen A vs regimen B.
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Constant TKI is NOT necessary in IO/TKI regimens. We need to prioritize strategies to de-escalate therapy for better QOL and possibly delaying resistance. Congrats to @DrIacovelli and the team for this important work.
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IMDC favorable risk RCC after #ASCO2023. Similar to ITT, early disease control for IO/TKI regimens and durability for Ipi/Nivo showing some favorable risk pts are immune-responsive. Biomarkers to select and to de-intensify treatment are needed. @Uromigos @montypal @DrChoueiri
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@Uromigos in São Paulo for a great conference. Here’s Tom and I preparing for our talks. Thanks to Fernando Maluf and all the great Brazilian oncologists. @FabioSchutz78 @fsabino_onco @DrAndreFay @SoaresAndrey
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Thank you @Uromigos podcast listeners on our 1 year anniversary! Almost 39,000 listens (only slightly more than the # of times @tompowles1 has interrupted me). Note after a year of hard work our podcast net worth is $0 🙃 Thanks to all our guests. #ASCOGU podcasts coming soon
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Updated table of int/poor risk mRCC including major monotherapy studies. IO/TKI comparable in early/tumor shrinkage endpoints vs Ipi/nivo but uncertain long-term durability. Role of monotx and how to select pts remains uncertain.
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Updated summary tables for the major RCC front-line trials incorporating @AlbigesL recent 48 month Ipi/nivo data plus IMDC subset data. Len/Pembro is the only missing piece.
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Sarcomatoid histology a good biomarker associated with greater benefit to adjuvant Pembro in RCC.
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VUMC starting a one-year GU Oncology Clinical Research Fellowship July 2021. More info here:
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Congrats to all authors for this comprehensive work defining the biology of mRCC. The next step is translating these data into clinically-actionable biomarkers through prospective trials.
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The best biomarker for ipi/nivo is sarcomatoid histology!.
⚡️ Long-term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma . @brian_rini @DrChoueiri @montypal @jitcancer #kidneycancer.
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KIM-1 is a novel prognostic and predictive biomarker in the adjuvant RCC space. Great data at #ASCO24 and stellar discussion by @VincentWenxinXu (Academy of Kidney Cancer Investigators member!). We discuss the KIM-1 data with @AlbigesL.
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Vanderbilt is leading the charge in doing biomarker-based RCC trials. Thanks to all supporting this effort. @KimrynRathmell @katy_beckermann @VUMC_Cancer @montypal @MosheOrnsteinMD @TiansterZhang #mikeatkins
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Neoadjuvant checkpoint inhibitor is powerful. We have not adequately tested this concept in RCC and need to do so urgently! #ASCO24
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So proud of my fellow Uromigo!!.
🎉Congratulations to BCI's Prof @tompowles1 who has been recognised by @TIME Magazine in their inaugural #TIME100HEALTH list of 100 individuals who most influenced global health this year for his breakthrough success in treating severe #bladdercancer. 📰
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Another point to clarify. The CR rate for axi/pembro is 9% as updated at asco. All these regimens are in the 8-10% range. More important is long term disease control eg the 30% profession free from 214 at long follow up. We need to expand our thinking of good response beyond CR.
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We knew PFS (and presumably ORR) would be positive given that Cabo/Nivo would beat Ipi/Nivo on tumor shrinkage endpoints. OS benefit needed and I worry an ‘immature’ OS will be like JAVELIN ie never positive. Remember IO/TKI OS HRs increased over time. Toxicity details critical.
Press release👉Cosmic-313 ph 3 trial in 1st line mRCC #kidneycancer meets primary endpoint: ⬆️PFS with cabozantinib+nivolumab+ipilimumab vs. Nivolumab+ipilimumab (HR: 0.73; 95% CI: 0.57-0.94; P=0.01). OS immature. @DrChoueiri @AlbigesL @OncoAlert Weblink:
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Some amazing correlate work form the IMmotion 151 study elucidating RCC biology. Congrats to the entire study team.
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@tompowles1 and I are at the amazing APCCC prostate meeting. Stay tuned for some special podcasts from Lugano!!
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#Hydroxychloroquine Pre-exposure prophylaxis study now open for high risk health care workers! @DrChoueiri @montypal @tmprowell please RT!
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Congrats to my new boss, friend and colleague @KimrynRathmell winning the lifetime achievement Schonfeld award from KCA. Well-deserved!!!
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Prospective cardiac monitoring and biomarker data from the JAVELIN RCC study now published on-line in JCO. Baseline Troponin T may be a marker for development of MACE on IO/TKI regimens. @ASCO @CardioOncology .
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The Academy of Kidney Cancer Investigators (AKCI) website is up and running! Check out to see the mentees, projects and how to apply through CDMRP.
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Thanks for helping @Uromigos podcasts reach 70,000+ total listens! Shout out to all of the guests on our 118 (and counting. ) podcasts. Many more to come and new endeavors including #Uromigovision launch.
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Apply now for our Vanderbilt GU Oncology Research Fellowship starting July 2024. Great opportunity for honing clinical and research skills!.
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Exactly. The responsibility falls to providers to give patients therapy with maximal benefit/risk. If no benefit, then it’s all risk. The persistence of this practice in the face of negative data is the desperation to help patients, but in fact results in more harm.
Does TiVo/nivo close the door on IO post IO? Why was the door ever open? Where is the data supporting continuing IO after failure? For desperate #kidneycancer patients, more always feels better. And far too many oncologists are happy to oblige given the high reimbursement rates
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Salvage Ipi/Nivo in IO-refractory RCC JCO article now on line: 20% ORR in line with recent trials of salvage Ipi after Nivo.
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Charis was a friend and trusted colleague during my time in Cleveland. She taught me a great deal about RCC genetics. The world of renal cancer and genetics is better because of her work.
This week, one of the deans of germline cancer genetics @CharisEngMDPhD passed away. She was the force behind research on the cancer predisposition syndrome PTEN Hamartoma Tumor Syndrome (PHTS), co-discovering the presence of germline PTEN mutations in individuals with Cowden
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Nice systematic review and meta-analysis of the association of prior nephrectomy and efficacy of IO-based doublets in mRCC. Prospective investigation is ongoing.
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Some caution about #hydroxychloroquine and a purely empiric approach to drug development in a time of crisis: Letters: Using Existing Medicines to Treat Covid-19 via @WSJ.
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PD-L1 is a very unreliable biomarker in RCC as it is in bladder cancer. We can and must do better to find predictive tools.
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Day 24 #RCCawareness: Ipi/Nivo is first IO-based combo to show advantages over sunitinib, paving the way for a new SOC in this disease. Durability is impressive. Biomarkers still elusive.
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Shout out to @VUMCurology for this recent analysis of the benefit of cytoreductive nephrectomy in the IO era:
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Day 26 #RCC awareness: Axi/Pembro was first IO/TKI combo to show benefits over sunitinib with advantages in OS/PFS/ORR in all IMDC risk groups. These data were an early signal of the IO/TKI data to follow.
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The Vanderbilt GU Program is looking for new faculty members. Clinical investigators with an interest in translational investigator-initiated trials across GU malignancies are preferred. Message me /@alantanmd for more details! Come work with stellar faculty in an amazing city!.
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#RCCawareness Day 8: Initial report that debulking nephrectomy improves OS in RCC. CARMENA data reinforces that patient selection is essential. Majority had lung-only mets and many had non-measurable mets -limited extra-renal tumor volume is important!
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Despite clinical data with limited impact, kudos to @genentech for a massive biomarker effort. Interesting hypotheses generated that require prospective testing. @VUMC_Cancer OPTIC trial coming soon to prospective test using clusters to assign therapy.
Final Overall Survival/Molecular Analysis in IMmotion151.🔶No OS difference.🔶Biomarker analyses 🧬may identify patients likely to benefit from combined anti−PDL-1 and anti–VEGF therapy. @JAMAOnc @OncoAlert @brian_rini @KidneyCancer @Uroweb @tompowles1 .
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This is one of many classic David McDermott eyerolls to Tom's comments during the RCC sessions of #UromigosLive. See the full videos here:.
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I guess you CAN harm patients with unproven therapy.
Pre-print: ChloroCovid trial of CQ + Azithro stopped early due to prolonged QTc and trend towards increased mortality in the higher dose (600mg BID) arm.
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There is no evidence of rebound after holding Axi. In fact, the short half life allows better long term tolerance (by employing periodic breaks) and quick resolution of any toxicity.
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Thanks to @JBrugarolas and his amazing team at #UTSW for their collaboration on this project. Surveillance and local approaches remain important in mRCC mgmt., and biomarkers to augment clinical selection criteria are important.
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Join us at the 2024 World Conference on GU cancers in New York this August. We look forward to hosting a Featured Session at this 2-day CE meeting and sharing the stage with world-renowned thought leaders. Register at: @GUconference #WorldGU24
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Enjoy this new review on an emerging therapeutic area in RCC: HIF inhibition.
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PD-L1 is less active than PD-1 directed agents in RCC, now including the adjuvant setting. Disappointing. Biomarkers desperately needed.
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Congrats to @KidneyCancerDoc and the entire team. This could revolutionize RCC mgmt as PSMA PET has done in prostate. In advanced RCC, using this post-systemic therapy in deep responders could inform stopping therapy and more intelligent application of local therapy to mets.
big news in RCC-hot off the press!!positive trial for CA9 pet/ct! thrilled to have our UCLA team be lead site. first of MANY initiatives- congrats to @TelixPharma team and special thanks to our patients. @UclaUrology @KidneyCancer @UCLAJCCC @montypal @neerajaiims @DrChoueiri.
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Day 30 #RCCawareness: Len/Pembro with the final IO/TKI dataset and perhaps the most impressive. @Uromigos podcast discussing IO/TKI regimens here:
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Come join the Vanderbilt team! We are looking for an early/mid-career GU Medical Oncologist with a bladder cancer focus.
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Thanks to Mike Atkins and the entire SITC RCC committee for their hard work on this document. Impressive advances since the last version!.
New #SITCGuidelines published in #JITC: “The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC)” includes recommendations on checkpoint inhibitors & more! #renalcell.
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Day 4 #RCCawareness: Seminal update of HD IL-2 data that led to FDA approval showing 5% CR rate, most durable. All CRs were ECOG 0 and s/p nephrectomy. Tumor burden didn't preclude CR and, depressingly, Table 5 fails to identify predictors of response - still true 25 years later
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Great faculty including @MattGalsky @DrRosenbergMSK @shilpaonc @UroCancerMD @JoshMeeks @PGrivasMDPhD @morr316 @DrRanaMcKay @TDorffOnc @neerajaiims @DrChoueiri @montypal @TiansterZhang @tompowles1 @Uromigos (and McDermott/Atkins not on X!). Thanks to our @GUOncologyNow partners!.
#UromigosLive is happening again! November 3rd and 4th in Nashville. Livestreams, podcasts, videos and lots of great content. Also, a HUGE trophy for the first annual Uromigos Cup. More details to follow!
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Academy of Kidney Cancer Investigator members @BraunMDPhD and @AChakrabortyPhD have collaborated on this excellent review of metabolic pathways in RCC. Go to for more info on the Academy and membership.
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#UromigosLive24 this Friday/Saturday. RCC session on front-line therapy in non-clear cell RCC will discuss SUNNIFORECAST and what is the SOC in papillary RCC. Podcast of the session to follow.
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Fun session and our community oncology panel was AMAZING. Thanks to Uramiga @DRathkopf for leading the prostate cancer portion.
🎙️ The Uromigos dive into "The Intersection Of Clinical Trials & Community Practice" with Drs. @brian_rini and @tompowles1 at 8:30 AM. Don’t miss this featured session! #WorldGU24 #CME #CE @Uromigos #CommunityPractice
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Depth of response analyses across RCC trials are beginning to show the same thing: more than CR patients benefit long-term.
Exploratory analysis of KN426 shows depth of response correlates with longer OS in axi pembro, not sunitinib in metastatic #kidneycancer @brian_rini @tompowles1 #ASCO20
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Adjuvant Pembrolizumab After Nephrectomy in Renal Cell Carcinoma: Embracing the Promises and Acknowledging the Uncertainties. #ASCODailyNews @ASCO
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Academy of Kidney Cancer Investigators Early Career Award now open! This virtual academy provides passionate, dedicated mentoring to clinical and translational investigators. Mentors include @montypal @Robert_Uzzo @JBrugarolas @AlbigesL.
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We are now accepting applications for our 2022-2023 GU Research Fellowship at Vanderbilt. Information here or DM me. Come be part of our robust team!. file:///C:/Users/rinib/Desktop/VUMC%20GU%20Fellowship%20Program%20Description%201.pdf.
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Day 16 #RCCawareness: COMPARZ trial of sunitinib vs pazopanib showing non-inferiority. In the end, providers picked their favorite TKI and gave it. Pretty sure same will happen with IO/TKI combos. Learn a regimen and give it well!
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Thanks to an amazing effort by @hemoncwarner and many others, the COVID-19 Cancer Consortium website is up and links to a redcap survey to gather data on COVID+ cancer patients. #COVID19.
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Thanks to all those who voted for me for the ASCO Nominating Committee. Last day to vote!
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Thanks to my great co-host @tompowles1 and to our amazing guests. It’s been quite a ride and the best is yet to come!.
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I think SBRT has a role in mRCC but remain unconvinced that it does anything to make IO work better.
NIVES study (SBRT + NIVO) failed to meet trial objective in RR. Is ipi needed to enhance abscopal effet ? @HHammersMD RADVAX RCC ORR 56%. Laurence.
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Check out our GU Fellowship available to start July 2023!.
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Neo/adjuvant nivo not effective in adjuvant RCC. I don’t think this is the final word on neoadjuvant IO in RCC. Difficult trial to conduct and some lessons learned.
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Thanks to a great friend and mentor Nick Vogelzang. He is the reason I am a GU oncologist and offers great perspectives in this podcast.
Nick Vogelzang gives an overview of developments in kidney cancer from the start and key moments in his career as part of the uromigos Legend weekly series.
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Thanks @wandering_gu and the entire Michigan Urology/GU Oncology crew. You have an amazing group who are stellar researchers and amazing people. I enjoyed my visit!!.
Amazing time hosting @brian_rini as the Montie-Shumaker visiting lecturer in RCC. Such a wealth of expertise in kidney cancer management, trials, and correlative science. So grateful for him making the trip up north! #GoBlue
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Annual in-person meeting of the AKCI starting soon! @BraunMDPhD @AChakrabortyPhD @JBrugarolas @TurajlicLab @montypal @AlbigesL @CDMRP
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First-line treatment of metastatic clear cell renal cell carcinoma: a decision-making analysis among experts - ESMO Open
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Important long term follow up for CM214. Integration of VEGF tx into this regimen could balance the initial need in angiogenesis high pts with durability of response. We need to better understand which patients to intensify and which to de-intensify.
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Shout out to Katy Beckermann for this article on a timely clinical topic. IO/VEGF is SOC in favorable risk RCC although more follow up and more data needed.
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Fun to debate Drs. McDermott and Atkins in this @TheLancetOncol editorial. All parties agree that biology-based treatment decisions are needed.
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Day 18 #RCCawareness: METEOR establishes cabozantinib as an effective refractory agent and reinforces that VEGF-targeted tx more effective than mTOR. High % of dose reductions balances toxicity and efficacy.
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Preparing for ESMO oral abstract discussion. How should ipilimumab be given in front-line mRCC? @tompowles1 @Uromigos @montypal @DrChoueiri @HHammersMD.
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