The Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute presents a succinct summary of all the kidney cancer clinical updates you need to know from ASCO GU 2023.
For those of you just joining us today. We're presenting updates from Oscar G 2023 Dr Xu will be discussing updates in kidney cancer with our esteemed discussing Dr Tony very um to give some expert commentary, Dr Xu. Take it away. All right, thanks very much Dr Burke Chuck. So I would summarize the kidney cancer experience at the G 2023 as we had interesting data from one new imaging biomarker which is during talks about pet and we had several practice affirming updates from ongoing clinical trials. But from the trial standpoint, I would hazard to say that for systemic therapy, there was data that was practice affirming but nothing that is yet to practice changing though certainly important updates. So I will start with the Zircon trial looking at a new joint tax map patch based imaging biomarker in clear cell kidney cancer. This trial presents the data from a phase three study of Zirconium joint taxi map for pet imaging. This is a novel imaging modality for clear cell kidney cancer and the data is presented by Dr The background for this is that the management of small renal masses still represents a bit of a clinical dilemma. Many patients with small renal masses go directly to surgery and out of the patients who do go to surgery. A significant minority, close to 20% ultimately are found to have benign findings despite a partial hysterectomy. In addition, not all patients who go through surgery and have small renal cell cancers will eventually have progression if they didn't have surgery. So the dilemma is between active surveillance biopsy versus surgery in these small renal masses. This trial looked at a novel imaging bomber could try to distinguish the patients who have clear cell kidney cancer versus other pathologies. Patients were eligible if they had a kidney mass that was seven centimeters or less. So, clinical T one on C T or M R I and they were scheduled for surgery. Patients had the tracer administered followed by imaging prior to surgery. Then patients had surgery and the results from the imaging were compared to the pathologic results. The co primary endpoints with the sensitivity specificity of this imaging modality versus central histology for detecting clear cell kidney cancer. Patient characteristics were similar to what you would expect from a small retail mass versus early stage clear cell kidney cancer population. Interesting to note that the majority of lesions or less than four cm and a significant minority were 4-7 cm. At the time of pathology. Most lesions were found to be clear cell kidney cancer and fewer percentages were found to be popular. Greek, Roma faux pas toma spindle cell sarcoma or other of note, the biomarker is not designed to distinguish between clear cell and non clear cell versus the nine but specifically clear cell versus all others. Looking at the co primary endpoints in this trial, the endpoints were assessed by three independent reviewers and the findings were consistent with all three reviewers showing high sensitivity and specificity for this imaging biomarker with a sensitivity in the 85, range and the specificity of 87%, this translated to a positive predictive value of 93% and a negative predictive value of 75%. So in other words, if the bond market was positive, it was very likely the mass was clear cell kidney cancer. If the biomarker was negative, it was still possible in some cases that it was still kidney cancer. A key secondary endpoint was a subset of patients with masses four cm or less. So these are T1 a small renal masses. The performance was similar in this key secondary endpoint sensitivity of 85.5% specificity 89.5%. So in summary, this novel biomarker zirconium joint taxi map had high sensitivity and specificity for distinguishing clear cell kidney cancer from other types of renal masses. Impressively, the performance was similar to better among patients with small renal masses compared to prior novel tracers for kidney cancer. This tracer is cleared by the liver and so overcome some of the difficulty with reno exclusion exclusion, seen with other pet tracers, the tracers was well tolerated and safety signals were minimal. Of note, it is still a bit of an open question where this imaging agent will fit into our clinical practice. It seems quite good at providing adjunctive information to support which patients with small renal masses might be had positive. In which case, they may not need a biopsy versus pet negative. In which case, a biopsy may still be needed to rule out either a uh false negative, clear cell kidney cancer or a non clear cell kidney cancer in this setting. Next, I'll go over updates from several important trials. I'll start with the outcomes by I M D C risk in cosmic 313, which was a trial evaluating Kabul plus naval plus B versus standard of care being evil plus placebo in intermediate or poor risk RCC. And this data was presented by Dr Powell's. This is an update to data that was previously presented by Dr Sherry at the recent asthma meeting PFS. Updated results of cosmic 313. Continue to confirm that there is a reduction in the reduction of risk of progression or death for the triplet compared to the doublet being evil evil in the intention to treat population. This is associated with a hazard ratio of 0.74. Looking at baseline characteristics by the I M D C risk. Interesting to note that prior to frack to me, among the poor risk patients was a little bit more common among patients receiving placebo versus patients receiving the triplet. And similarly, the rate of target lesions in the kidney was a little bit more common in the patients were receiving the triplet. When we break down by I M D C risk group, we find results that are consistent with what we initially saw based on the initial presentation of cosmic 313, essentially the triplet performed a little bit better in the intermediate risk group compared to the poor risk group. Compared to it being evil. Looking at the intermediate risk patients, there was a 32% reduction in the risk of progression or death, whether has a ratio of 0.68. However, in the poor risk group that has a ratio was 0.93 with the confidence intervals crossing one. So for whatever reason, it continues to appear that the triplet performs better in intermediate versus poor patients. Next, we look at two more response by I M D C risk. The overall response rate was 36 versus 38% in the poor risk patients and 45 versus 36% in the intermediate risk patients. Again, the overall response rate favors the triplet in the intermediate risk patients but not in the poor risk patients worth noting that the disease control rate was high and it was better for the triplet in all groups. So why is it that the intermediate risk patients seem to benefit more from the triplet? One hypothesis could be that the intermediate risk patients perhaps received more dilemma map in the placebo arm compared to the triplet arm. But it turns out that when you compare the intermediate to poor risk, 74% of patients and intermediate risk receiving placebo Received four doses of IPI versus 55% receiving a triplet. So similarly, in the poor risk, there was no difference in the number of doses of it be received between the triplet and doublet. So this does not seem like an adequate explanation for the findings of the different response rates between intermediate versus poor risk for Kabul had been evil. Another explanation could be that the biology of I M D C intermediate risk is not the same as the biology of poor risk and perhaps the intermediate risk tumors were more and genetically driven and therefore benefited more from the addition of Kabul's antonym. Overall data remains immature at this time. And so as an event driven endpoint, we have to give further time for that data to mature. Next, I'll talk about updates to checkmate nine which was a trial investigating the volume up and caboose and turnip in the metastatic setting compared to some catnip. This data was presented by Dr Dorado. Previously, we know that checkmate 90 are demonstrated pfs and OS superiority for the doublet of Kabul plus Nevel compared to synonym at 44 month. Follow up outcomes continue to favor Nevada map plus cables, antonym for both PFS and OS with PFS has a ratio of 0.58 and OS has a ratio of 0.7 looking at PFS by I M D C risk. There is a trend towards improved PFS among all I M D C subgroups but the trend is stronger among the poor risk patients and a little bit less strong among the favorable risk. And indeed looking at the favorable risk subset, the PFS hydro ratio crosses one in the subgroup analysis. Looking at OS, this is quite interesting data and it's consistent with what we've seen across this and also other I O T K I trials. It appears that overall survival continues to strongly favor the doublet naval capital compared to in the poor risk patients and an intermediate risk patients in the favorable risk patients. It's less clear that there is an overall survival difference. Although keeping in mind, this is a subset analysis, the hazard ratio for overall survival in a favorable risk population is 1.7 with, with a confidence interval. Um coming around one, looking at best overall response by I M D C risk. The overall response rate does favor the doublet in all subsets. Finally, this included analysis of the time the subsequent therapy for patients who completed two years of development on checkmate, nine er patients were limited to two years of development maximum and afterwards continued cables antonym on its own. And the time the subsequent therapy was reassuring at a long 20.6 months for patients who were able to complete the two years of therapy suggesting that there are some durable responses. So what does this add these two trials to our current Armamentarium in the first line for RCC? I would argue that these results are not immediately practices changing for now. The standard of care remains one of the doublet immunotherapy containing regiments, Naval land, Pembroke or Oxy Pembroke. And overall survival data from cosmic 313 when available might move the needle. Next I will discuss Cable Point. This was presented by Dr Albert Baez and was a phase two study looking at cables antonym after prior immunotherapy in patients with advanced renal cell carcinoma. Cable point was a European trial that included two cohorts patients who had received first line being evil followed by cables and second line or patients who received a IOT K I combination followed by second line cables and turnip. Patient characteristics are displayed here In the interim efficacy analysis. There was overall a close to 30% overall response rate for Campbell's entities in both cohorts. The overall response rate was a little bit higher among patients who received prior. It being evil compared to patients who received an IOTKI. But this difference had overlapping confidence intervals. The cable point data reinforces what we know about T K I S in the second line setting. I want to especially point out that this is very close to what we saw from the prior canta data with cables antonym in the second line setting. And uh the other measurements that we have refractory data for are shown here just for completion. Next Dr mcgregor presented updates on cosmic 0 to 1 for cables and in combination with the table is a map and non clear cell renal cell carcinoma, cohort 10, we know that Cabo A Tiso has activity in non clear cell kidney cancer with an overall response rate in this data of 31%. Um This data is still maturing, but it's important to point out that we also no doubt that contact three failed to meet its PFS endpoint in a press release. Although data from contact three has not yet been released in this cohort, we show that um there are responses among various clear cell and various non clear cell subtypes but more among the popularity and unclassified patients. Dr Sherry presented a biomarker analysis from the phase three checkmate nine er trial which we just discussed. This trial had preplanned biomarker analysis including I H C and R N A C based market analysis we found in Checkmate nine er according to data presented by Dr Sherry that Hallmark gene sets were associated with progression free survival outcomes for Naval Kabul versus and the particular gene sets are shown here. Interestingly when the authors investigated specific RNA gene expression signatures including prior signatures that were described in the table BEV. And the actually available map studies, none of the seven published gene expression signatures predicted PFS with Naval Cabo versus unit NIB. Looking at two more PDF one consistent with prior data among the senate patients, patients with high PD L one expression did worse. However, PD L one status was not associated with PFS and then the vocab alarm and this suggests that response to Nepal A mob may have improved the outlook of some of these patients. Next, I'll review an update from H C R N G U 16 to 60 cohort A which was presented by Dr Michael Atkins. This looked at treatment free survival from a phase two study of Negro Cable. Uh sorry, I'm level and salvage the volume map and map and patients who have subsequent progression treatment free survival is an interesting new endpoint looking at the time that patients spend both not progressing and uh both alive and not on treatment. So this is the end point that's really tilted towards patient preferences and the ability to have normal time not receiving anticancer treatment after prior therapy. Look at survival states, 65.6% of patients among the favorable risk subset were alive and subsequent treatment free at 36 months, 27% of patients were alive and treatment free at 36 months among the intermediate and poor risk patients. Interestingly, this data compares favorably to the previous reported data from checkmate 214 in this trial, which started with the volume at as opposed to it being evil and check my 214 treatment free survival appeared better and longer compared to the open evil data. However, I want to point out that the patient numbers are small and so this data should be considered exploratory for the interest of time. I'll go quickly over the bionic trial. This was an update for overall survival and second line treatment for patients who are grouped by molecular subgroup based on transcriptome signatures. And then based on the subtype randomized to either nevel versus the ability for C C R T C one and four or naval IPI versus 80 K I. Overall survival showed that among patients with clear cell RCC for the overall response rate was 55% for naval P versus 44% for novel A mob. And in patients with clear cell RCC too, The overall response rate was higher with TKI compared to with the validity. Nonetheless, we look at the survival curves. Um there does look like there's a trend towards better overall survival although not significant with the validity even in the CCRCC two subgroup. Second line therapy interestingly continued to be informed by the molecular subtype and among patients who are see CRC C four, uh second line treatment, post overall response rate was a little bit higher compared to post level. And among see CRC C to the overall response rates were similar post T K I and post being evil. Finally, in the last 30 seconds, I want to highlight work that was done by Dr Labaki in our own group, mentored by Dr Sherry, looking at characterization of clinical outcomes in patients with chroma foam RCC. This work was done in the I M D C database and reinforces our prior clinical knowledge by chromosome RCC where it appears to have worse overall survival and worst type of treatment failure when treated with immunotherapy regimens, but does have some responses to T K I therapy. And with that, I will open this up to discussion and invite Dr Sherry to give comments on the kidney cancer abstracts. Thanks, Vincent, great work. Really nothing earth shattering uh Presented happy that the median overall survival. Now, you know, with more follow up, you have to be careful when you say medium because sometimes you know, they're the same, you have to look at the shape of the girls. Now we have suddenly almost a year difference on 90 are so that was good. I think it's important people to understand why we had triplet um you know, doing better in the intermediate risk. One idea was that maybe the triplet arm at baseline had more worse characteristic at baseline. That is not true or maybe maybe the triplet arm didn't have enough Kabul or enough it be compared to the doublet and that was not true. The rest is just simple and provided all your comments. Well, fantastic. Well, thanks Dr Xu. Thanks Dr Sherry.
