Feb 18, 2021
In today’s episode, Dr. Stephen Boorjian, professor of urology at the Mayo Clinic, in Minnesota, and chair of the GU Cancers Symposium, discusses key advances across GU malignancies.
ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Stephen Boorjian, professor of urology at the Mayo Clinic in Minnesota and chair of the 2021 Genitourinary Cancer Symposium. Dr. Boorjian joins me to discuss new developments in the GU field featured at the meeting. Dr. Boorjian serves as a consultant for Ferring, FerGene, and ArTara. Full disclosures relating to all episodes of the podcast are available on our transcripts at ASCO.org/podcasts. Dr. Boorjian, it's great to have you on the podcast today.
Dr. Stephen Boorjian: Thank you very much. It's a privilege to be here and I'm happy to participate.
ASCO Daily News: There was a lot of interest in the CheckMate 274 trial. What can you tell us about this study and its likely impact on the future management of patients with muscle invasive urothelial carcinoma after radical surgery?
Dr. Stephen Boorjian: Absolutely. Thanks, Geraldine. So this trial was presented in Abstract 391. This was the first results released from this phase III randomized, double blind, multicenter clinical trial. The trial tested adjuvant therapy with the immune checkpoint agent nivolumab versus placebo in patients with muscle invasive urothelial carcinoma following radical surgery. This was a trial that enrolled over 700 patients. Patients were randomly assigned in a one to one fashion for 1 year of treatment. The primary endpoints of the trial were disease-free survival in all patients, as well as in patients with tumor expression of PD-L1 ≥ to 1%.
Very importantly, the primary endpoint of disease-free survival was met in both of those study cohorts, specifically in the intention-to-treat population. The median disease-free survival in the patients treated with nivolumab was 21 months versus 10.9 months in the placebo arm. And that result was highly statistically significant. Likewise, in the cohort of patients with PD-L1 expression ≥ 1%, the median disease-free survival was actually not reached in the nivolumab arm versus 10.8 months in the placebo arm. And again, highly statistically significant.
Grade 3-4 treatment-related adverse events in the study occurred in 17.9% and 7.2% in nivolumab and placebo arms, respectively. I selected this trial for highlighting because I believe this has the potential to significantly impact future management of these patients' [disease]. The role of adjuvant therapy after radical surgery in urothelial carcinoma has remained very poorly defined. These results, I should say, really represent an opportunity, I think, for our patients to now receive an adjuvant therapy with demonstrated subsequent efficacy in the median disease-free survival, as we saw.
ASCO Daily News: It's great to hear about such promising data on the role of adjuvant therapy for this patient population. Moving on to the SEMS trial, Abstract 375. This study reported promising results for a young patient population with early metastatic seminoma. You were a co-investigator on this trial. What can you tell us about it?
Dr. Stephen Boorjian: So Abstract 375 reports the results from a Phase II multi-institutional surgical trial in early metastatic seminoma. What was particularly exciting to me about this trial is it gave the opportunity to incrementally impact a long-held management paradigm and to change it. So the management for patients with early stage metastatic seminoma has historically been with radiotherapy or chemotherapy, and each of these carry with them the potential for long-term adverse side effects in what is otherwise a very young and healthy patient population.
So this trial tested the use of retroperitoneal lymph node dissection, so surgical resection, in patients with early metastatic seminoma. It accrued at 12 sites in the United States and Canada. Patients had isolated retroperitoneal lymphadenopathy between one and three centimeters and testicular seminoma. The primary endpoint of the trial was 2-year recurrence-free survival. Fifty five patients were enrolled in the trial and with a median follow-up of 24 months, the overall recurrence rate was 18% for a 2-year recurrence-free survival of 87% and overall survival of 100% There were only two Clavien [Dindo] grade 3 complications in the perioperative period and no long-term complications associated with it.
So I think this trial has the potential to establish retroperitoneal lymph node dissection as a therapeutic option in first-line therapy for early metastatic seminoma. It's effective. It's safe in both the short and the long term. And I was really privileged to be part of a surgical trial, which can be often quite difficult to conduct. And I want to congratulate Dr. Daneshmand, the trial's principal investigator.
ASCO Daily News: Absolutely. Focusing on kidney cancer for a moment, can you tell us about the CLEAR study--that's Abstract 269--and the opportunity it represents to offer another potential first-line therapy to patients with advanced renal cell carcinoma?
Dr. Stephen Boorjian: Sure. So Abstract 269 reported the phase III trial, which was a three-armed prospective randomized trial for patients with advanced renal cell carcinoma. These patients were randomly assigned in the study to receive either the combination of lenvatinib and pembrolizumab, or lenvatinib and everolimus, or sunitinib. The primary endpoint of the study was progression-free survival. And the study was targeted at patients with no prior systemic therapy. So this was a first-line therapy trial.
The trial enrolled over 1,000 patients, and with a median follow-up of 27 months, the trial demonstrated that progression-free survival was significantly improved among patients who received the combination of lenvatinib and pembrolizumab at 24 months versus sunitinib at 9 months. Likewise, the complete response rate in the cohort of patients treated with the combination of lenvatinib and pembrolizumab was 16% compared to 4% with patients treated with sunitinib. And the median duration of response was quite durable at 26 months among the lenvatinib-pembrolizumab arm.
So the trial was exciting to me as an opportunity to bring forth another potential first-line therapeutic management strategy for patients with advanced renal cell carcinoma. I think as we continue to evolve in this field, treatment selection will depend on biomarkers as they continue to be explored and developed, differences in side effects, [and] patient tolerability profiles. So I think having one more option in the armamentarium can only help to benefit our patients going forward.
ASCO Daily News: Indeed. There were multiple studies about the impact of health disparities. Abstract 14 is really interesting because it provides a real-world snapshot of the genomic landscape of advanced prostate cancer in a hospital that serves racial and ethnic minority communities. The study highlights the importance of next generation sequencing in guiding therapies for these patients. So improving access to this care is crucially important. What are your thoughts on this study?
Dr. Stephen Boorjian: Abstract 14, I thought, highlights a very important and very timely topic and that is to evaluate the genomic landscape of advanced prostate cancer in racial minority populations. It used a real-world safety net hospital experience and demonstrated higher frequencies of androgen receptor as well as other homologous recombination repair gene mutations in African-American cohort compared to patients with prostate cancer of other races and ethnicities.
As the study utilized next generation sequencing, I thought the approach was quite elegant. And I think, ultimately, this demonstrates the potential importance of that type of next generation sequencing strategy to guide therapy as we move more and more towards targeted therapies in patients with advanced prostate cancer. And I think it emphasizes the need to decrease barriers to access to such types of investigative modalities such as next generation sequencing for racial minorities. So I liked the fact that that abstract sort of specifically brought forth a couple of different themes around a very important and timely topic.
ASCO Daily News: Absolutely. Staying in the prostate cancer space, a University of California Health System registry study looked at androgen deprivation and the risk of COVID-19 infection in men with prostate cancer. This is a very timely topic. Can you tell us about it, Abstract 37?
Dr. Stephen Boorjian: Yeah, Abstract 37, I thought again, addressed a very timely topic in 2020 and 2021, which was the association of men receiving androgen deprivation therapy with COVID-19 infection. So we are getting lots of questions about the potential interaction of cancer diagnosis and cancer therapies and COVID-19 diagnosis, and this study, which was conducted using a retrospective registry of adult men with prostate cancer in the University of California Health System, evaluated the correlation between COVID-19 diagnosis and androgen deprivation therapy use.
Androgen deprivation therapy is a baseline therapy for men with advanced prostate cancer used quite frequently. And therefore, understanding the potential interaction that androgen deprivation therapy might have with COVID diagnosis is important for patient counseling and treatment going forward. And in fact, what the study found was no association between the use of androgen deprivation therapy and the risk of testing positive for COVID-19 in their patient cohort population.
And I think that can be looked at in one of two ways. Androgen deprivation therapy is not protective, based on these data, against COVID-19 infection, as it might have been speculated to be because of intracellular expression modification. But at the same time, there wasn't a negative association, and there was no increased risk of COVID-19 diagnosis noted among men receiving androgen deprivation therapy. So I think this sort of can help us going forward, as we understand more and more about the potential interactions of our cancer therapies with COVID-19 diagnosis.
ASCO Daily News: Dr. Boorjian, Thanks so much for taking the time to share these really interesting highlights from the GU Cancer Symposium with us.
Dr. Stephen Boorjian: Thanks very much for having me. It is my pleasure.
ASCO Daily News: And thanks to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate and review us wherever you get your podcasts.
Disclosures: Dr. Stephen Boorjian
Consulting or Advisory Role: Ferring, Sanofi, ArTara, FerGene
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