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).
Transcript
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.
Lisa A. Carey, MD, of the University of North Carolina Lineberger Comprehensive Cancer Center, and Hope S. Rugo, MD, of the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, discuss phase III results from the TROPiCS-02 trial. This study showed that sacituzumab govitecan-hziy was more beneficial than single-agent chemotherapy in terms of progression-free survival in heavily pretreated patients with hormone receptor–positive/HER2-negative and unresectable advanced breast cancer (LBA1001).
Paul G. Richardson, MD, of Dana-Farber Cancer Institute, discusses phase III findings from the DETERMINATION trial, which showed that, for patients with newly diagnosed multiple myeloma, lenalidomide, bortezomib, and dexamethasone (RVd) with or without autologous stem cell transplant (ASCT) and lenalidomide maintenance to disease progression resulted in the longest median progression-free survival reported for each approach, and a highly significant difference in progression-free survival in favor of early transplant. While overall response rates were similar, rates of MRD favored early transplant also, but toxicity was greater and quality of life was transiently but significantly diminished. No overall survival advantage has been observed to date (Abstract LBA4).
The ASCO Post Staff
Sriram Yennu, MD, of The University of Texas MD Anderson Cancer Center, discusses the placebo response in patients with advanced cancer and cancer-related fatigue. His latest findings show that open-labeled placebo was efficacious in reducing cancer-related fatigue and improving quality of life in fatigued patients with advanced cancer at the end of 1 week. The improvement in fatigue was maintained for 4 weeks (Abstract 12006).
The ASCO Post Staff
Erika Hamilton, MD, of Sarah Cannon Research Institute at Tennessee Oncology, discusses phase III data from the DESTINY-Breast03 study, which reinforced the consistent safety profile of fam-trastuzumab deruxtecan-nxki (T-DXd) vs ado-trastuzumab emtansine (T-DM1) in patients with HER2-positive unresectable and/or metastatic breast cancer. The findings also support T-DXd’s risk benefit over that of T-DM1 (Abstract 1000).
The ASCO Post Staff
Andrew D. Zelenetz, MD, PhD, of Memorial Sloan Kettering Cancer Center, and Michael L. Wang, MD, of The University of Texas MD Anderson Cancer Center, discuss primary results from the phase III SHINE study, which showed that ibrutinib, in combination with bendamustine/rituximab and rituximab maintenance, may set a new benchmark for patients aged 65 or older with mantle cell lymphoma. With a median progression-free survival of 6.7 years, the ibrutinib combination is more beneficial than currently used chemoimmunotherapy (approximately 1.5–3.5 years) (Abstract LBA7502).