Don S. Dizon, MD, on Ovarian and Other Extrarenal Clear Cell Carcinomas: Update on Nivolumab and Ipilimumab
2024 ASCO Annual Meeting
Don S. Dizon, MD, of Legorreta Cancer Center at Brown University and Lifespan Cancer Institute, discusses final phase II results of the BrUOG 354 trial showing that, for patients with ovarian and other extrarenal clear cell cancers, nivolumab and ipilimumab warrant further evaluation against standard treatment, given the historically chemotherapy-resistant nature of the disease (LBA5500).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
I will be presenting BrUOG 354 which is a two-arm randomized non-comparative clinical trial that enrolled people with extrarenal clear cell carcinoma. And tested two regimens, both of them immunotherapeutic. One used nivolumab alone, and the other used nivolumab plus ipilimumab. We enrolled 46 people to this trial, 44 of whom were treated. All of these patients had a diagnosis of clear cell cancers of the gynecological tract. And that's important because clear cell cancers when you compare them to the more common serous type cancers, are associated with a worse prognosis. They do not respond as well to our standard chemotherapies, are prone to relapse more frequently. And unfortunately in the context of recurrent disease, they do not respond as well to treatment. So the prognosis is actually quite poor. This prompted this clinical trial. And it was actually based on some very preliminary data where people were seeing clinical complete responses in folks with clear cell cancers.
To this point, before this trial was presented, there had been two trials of immunotherapy in ovarian cancer. One suggesting that clear cell cancer was associated with a five-fold higher response rate compared to other histologies. Although that clinical trial which was done by NRG Oncology group, only enrolled 12 people with clear cell. For that, suggestion was made. And the other was a SWOG clinical trial that enrolled 18 people with ovarian cancer and showing that the combination of nivolumab and ipilimumab was effective with some durability, again, based on a very small number of patients. So our trial which enrolled 46 people, is the largest trial in this very rare cancer population.
What we can report is that both single-agent nivolumab, and nivolumab and ipilimumab have activity in clear cell cancers, and both are associated with survival outcomes although the one with combination therapy is longer. The overall response rate with single-agent nivolumab is 13%, which includes two partial responses. Median progression free survival is two months, and median overall survival in this trial was less than six months. With the combination therapy, the overall response rate was 33% with five complete responders. Median progression free survival in that arm was 17 months, and median overall survival is 24 months. And importantly for those who responded to the combination, the response was durable. And we had several patients who remain on study past two years, including up to today.
The ASCO Post Staff
Sherene Loi, MD, PhD, of Peter MacCallum Cancer Centre, discusses a circulating tumor DNA (ctDNA) analysis from a cohort of patients with early-stage breast cancer who were enrolled in the monarchE trial. This large cohort was studied to look at the usefulness of a personalized tumor-informed assay for ctDNA detection in early stage high-risk patients (LBA507).
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Efrat Dotan, MD, of Fox Chase Cancer Center, discusses results from the phase II EA2186 trial, the first prospective study aiming to define the optimal treatment approach for vulnerable older adults with newly diagnosed metastatic pancreatic cancer (Abstract 4003).
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Alicia Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Susan Halabi, PhD, of the Duke Cancer Institute and Duke University School of Medicine, discuss a clinical-genetic model that identified novel circulating tumor DNA alterations that are prognostic of overall survival and may help to classify patients with metastatic castration-resistant prostate cancer into risk groups useful for selecting trial participants (Abstract 5007).
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Toni K. Choueiri, MD, FASCO, of the Dana-Farber Cancer Institute, discusses phase III findings showing that, in patients with advanced renal cell carcinoma (RCC), the benefit of lenvatinib plus pembrolizumab vs sunitinib in overall response rate does not appear to be affected by such factors as gene‐expression signatures for tumor‐induced proliferation, PD‐L1 status, or the mutation status of RCC driver genes.
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William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center, discusses up to 5.5 years of follow-up data from the phase II CAPTIVATE study, showing that in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), fixed duration ibrutinib plus venetoclax continues to provide clinically meaningful progression-free disease in those with high-risk genomic features as well as in the overall population (Abstract 7009).