Sumanta K. Pal, MD, on Urothelial Carcinoma: New Results on Cabozantinib Plus Atezolizumab
2022 ASCO Annual Meeting
Sumanta K. Pal, MD, of City of Hope National Medical Center, discusses findings from the COSMIC-021 study, which showed that cabozantinib plus atezolizumab demonstrated encouraging clinical activity with manageable toxicity in patients with inoperable locally advanced or metastatic urothelial carcinoma. The combination was administered as first-line therapy in cisplatin-based chemotherapy–eligible and –ineligible patients and as second- or later-line treatment in those who received prior immune checkpoint inhibitors (Abstract 4504).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The COSMIC-021 study is a trial that includes multiple different histologies, multiple different cohorts. At this year's ASCO meeting, ASCO 2022, I presented data pertaining to cohorts three, four, and five. This specifically looked at patients with advanced urothelial carcinoma. The composition of each of the cohorts was distinct. In cohort three, we had patients that were cisplatin-ineligible. In cohort four, patients that were cisplatin-eligible. And finally, in cohort five, patients that had received prior immune checkpoint inhibitors. What ultimately it boiled down to is about 30 patients per cohort. In terms of the distribution of patients, it was predominantly male, as you might expect. Most of the patients had a bladder primary, although we did actually have good representation of upper track tumors, ureteral tumors, and so forth. That was about 30% of the study population. Amongst those patients that had received prior immune checkpoint inhibitors, about 30% had received one prior therapy implying immune-based treatment, and about 68% had received two or more prior lines of treatment. What we saw was actually a graded response. In patients who were cisplatin-eligible we saw the highest response rate, 30%. In patients that cisplatin-ineligible we saw a response rate of 20%. And finally, in patients that had received prior immune checkpoint inhibitors, we saw a response rate of 10%. It's always tricky to know what endpoints to follow in these relatively small studies. One thing that really I found intriguing was the duration of response. And with substantial follow up at this point in time, we still haven't reached the median duration of response amongst those patients that were cisplatin-eligible. I really think that the toxicity profile that we saw in this study really mimics what we've seen in other experiences of cabozantinib with atezolizumab. The combination seems to be very well tolerated. We used a dose of cabozantinib at 40 milligrams. The rates of hepatitis, the rates of other toxicities that you'd expect with a combination like diarrhea, were very reasonable and manageable by and large. So in summary, I think that this combination really does have activity. My hope is that we'll be able to study it further in certain contexts. And in particular, there's a study ongoing right now that I'll plug, MAIN-CAV through the Alliance. It's led by Dr. Shilpa Gupta. This trial I think is a prime way for us to understand the role of cabozantinib with immunotherapy where that combination's being assessed in the maintenance setting.
Robert Hugh Jones, MD, PhD, of Cardiff University and Velindre Hospital, discusses results from an updated analysis of the FAKTION trial, which showed improved overall survival with fulvestrant plus capivasertib in women with metastatic estrogen receptor–positive breast cancer whose disease had relapsed or progressed on an aromatase inhibitor. The benefit may be predominantly in patients with PIK3CA/AKT1/PTEN pathway–altered tumors, a topic researchers continue to study in the phase III CAPItello-291 trial (Abstract 1005).
Lisa A. Carey, MD, of the University of North Carolina Lineberger Comprehensive Cancer Center, and Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center, discuss the phase III findings from the DESTINY-Breast04 trial, which compared fam-trastuzumab deruxtecan-nxki (T-DXd) vs treatment of physician’s choice (TPC) in patients with HER2-low unresectable and/or metastatic breast cancer. T-DXd is the first HER2-targeted therapy to demonstrate clinically meaningful improvement in progression-free and overall survival compared with TPC in this patient population, regardless of hormone receptor or immunohistochemistry status or prior use of CDK4/6 inhibitors (Abstract LBA3).
Ann H. Partridge, MD, MPH, of Dana-Farber Cancer Institute, and Véronique Diéras, MD, of the Centre Eugène Marquis, discuss the many challenges posed by next-generation antibody-drug conjugates (ADCs). They include side effects such as hematotoxicity, gastrointestinal toxicities, and interstitial lung disease; tumor targeting and payload release; drug resistance; and the urgent need to understand ADCs’ mechanisms of action to better sequence and combine drugs.
Courtney D. DiNardo, MD, MSCE, of The University of Texas MD Anderson Cancer Center, and Jorge E. Cortes, MD, of Georgia Cancer Center at Augusta University, discuss phase III results from the ASCEMBL trial, which showed that after more than 2 years of follow-up, asciminib continued to yield superior efficacy and better safety and tolerability vs bosutinib in patients with chronic myeloid leukemia (CML) in chronic phase. These results continue to support the use of this kinase inhibitor as a new CML therapy, says Dr. Cortes, with the potential to transform the standard of care (Abstract 7004).
Jonathan E. Rosenberg, MD, of Memorial Sloan Kettering Cancer Center, and Thomas Powles, MD, PhD, of Barts Health NHS Trust, Queen Mary University of London, discuss phase III findings from the KEYNOTE-426 trial, which appear to support the long-term benefit of pembrolizumab plus axitinib for first-line treatment of patients with advanced clear cell renal cell carcinoma (Abstract 4513).