Bradley McGregor, MD

Bradley McGregor, MD, clinical director, Lank Center for Genitourinary Oncology, senior physician, Dana-Farber Cancer Institute, and instructor of medicine, Harvard Medical School, discusses the ongoing COSMIC-313 trial (NCT03937219) of cabozantinib (Cabometyx), ipilimumab (Yervoy), and nivolumab (Opdivo) in patients with renal cell carcinoma (RCC).

COSMIC-313 is a randomized trial of this combination compared with nivolumab and ipilimumab. In this setting, there are many different VEGF inhibitors and immune-oncology (IO) combinations with slightly different toxicity profiles and different drugs. There are also IO-IO combinations—for these, it seems like there are a group of patients who have a durable response and are able to go off of therapy, according to McGregor. It is uncertain if this response will be seen with VEGF and IO combinations since those data are still maturing. With IO-IO combinations for patients with RCC, over 20% have progressive disease as their best response.

McGregor says the hope with COSMIC-313 is that the triplet combination of nivolumab and ipilimumab with cabozantinib will be able to overcome the progressive disease as best response for these patients. He also hopes that this combination will maintain a point where patients can continue on therapy and have durability of their response.

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Bradley McGregor, MD, discusses the ongoing COSMIC-313 trial of cabozantinib, ipilimumab, and nivolumab in patients with renal cell carcinoma.

Combination of Cabozantinib/Ipilimumab/Nivolumab Investigated in RCC

Bradley McGregor, MD, clinical director of Lank Center for Genitourinary Oncology, senior physician at Dana-Farber Cancer Institute, and instructor of Medicine at Harvard Medical School, discusses the CheckMate-9ER trial (NCT03141177) of nivolumab (Opdivo) plus cabozantinib (Cabometyx) versus sunitinib (Sutent) in patients with previously untreated advanced or metastatic renal cell carcinoma (RCC).

This trial enrolled patients from all of the International Metastatic RCC Database Consortium risk groups. The number of patients in each risk were comparable to real-world practice according to McGregor, with 20% to 25% having favorable risk, about 60% having intermediate risk, and about 20% having poor risk. The patients were evenly distributed through the United States, Europe, and the rest of the world.

The data from the initial analysis showed that there was a marked improvement in progression-free survival (PFS) at a median follow-up of 18 months. This improvement produced a hazard ratio of 0.51, with a median PFS of 16.6 months with the combination versus 8.3 months with sunitinib. The overall survival has not been reached in either group, but the hazard ratio favors the combination at 0.60. McGregor says the P value was also statistically significant. The subgroups also favored nivolumab and cabozantinib in this study.

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Bradley McGregor, MD, discusses the CheckMate-9ER trial of nivolumab plus cabozantinib versus sunitinib in patients with previously untreated advanced or metastatic renal cell carcinoma.

CheckMate-9ER Shows Efficacy of Nivolumab/Cabozantinib Combo in RCC

Bradley McGregor, MD, clinical director, Lank Center for Genitourinary Oncology, senior physician, Dana-Farber Cancer Institute, and instructor of medicine, Harvard Medical School, discusses a small study that evaluated the combination of atezolizumab (Tecqntriq) and bevacizumab (Avastin) for the treatment of patients with non-clear cell renal cell carcinoma (RCC).

As much as the treatment landscape has evolved for advanced RCC over the last several years, these efforts have been mainly focused on clear cell RCC, says McGregor. The majority of trials exclude patients with non-clear cell variant histology RCC, but retrospective data have shown these patients tend to do worse.

In an investigative response trial, McGregor says the combination of atezolizumab plus bevacizumab was evaluated in this patient population of 60 patients, 42 of which had variant histology RCC and 18 had clear cell RCC with sarcomatous differentiation.

About half of the patients with variant histology RCC had received prior systemic therapy, McGregor notes. The overall response rate in all patients was 33% and 26% independent of histologic type. McGregor says the patients with chromophobe had the lowest response rate, but the regimen was well-tolerated with minimal grade 3 or higher adverse events.

Bradley McGregor, MD, discusses a small study that evaluated the combination of atezolizumab and bevacizumab for the treatment of patients with non-clear cell renal cell carcinoma.

Using Combination Therapy as Treatment of Non-Clear Cell RCC

Bradley McGregor, MD, clinical director of Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, discusses a trial investigating atezolizumab (Tecentriq) and bevacizumab (Avastin) in patients with metastatic renal cell carcinoma (RCC) and variant histologies and/or sarcomatoid features.

McGregor thinks that much of the data over the last few years has been focused on clear cell RCC, with trials like CheckMate-214; data from studies of pembrolizumab (Keytruda) and axitinib (Inlyta), or axitinib and nivolumab (Opdivo) excluded patients with non-clear cell and variant histology RCC. These patients do not do as well as patients with clear cell RCC, so McGregor and his colleagues started an investigator&rsquo;s response trial. The purpose of this trial was to evaluate the combination of a VEGF inhibitor and an immune checkpoint blockade in patients with variant histologies or clear cell histology with sarcomatoid features.

The trial had a total of 60 patients, who received atezolizumab and bevacizumab based on the IMmotion 150 and 151 data. McGregor say this regimen was appealing because it was well tolerated by patients in those trials. Patients in this trial were given the standard dose of atezolizumab and 15 mg/kg of bevacizumab every 3 weeks. Patients were allowed to have prior therapy, which he says was unique for this setting. Over 1 and a half to 2 years, the study enrolled the 60 patients; 42 patients had variant histology RCC and 18 had clear cell RCC with sarcomatoid differentiation.

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Bradley McGregor, MD, discusses a trial investigating atezolizumab and bevacizumab in patients with metastatic renal cell carcinoma and variant histologies and/or sarcomatoid features.

Atezolizumab and Bevacizumab Studied in Patients With Metastatic RCC

Bradley McGregor, MD, clinical director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, senior physician, instructor in medicine, Harvard Medical School, discusses the goals of the phase III CheckMate-9ER trial, which is evaluating cabozantinib (Cabometyx) combined with nivolumab (Opdivo) in previously untreated patients with advanced or metastatic renal cell carcinoma (RCC).

There has been a revolution in RCC treatment over the last couple of years, starting with the immunotherapy combination of nivolumab and ipilimumab (Yervoy) in the CheckMate-214 trial. Cabozantinib is an intriguing multikinase inhibitor that has also demonstrated benefit in patients with both treatment-na&iuml;ve and previously treated disease, McGregor says.

Building upon the activity with these types of agents in the frontline setting, the CheckMare-9ER trial is looking at the combination of cabozantinib and nivolumab compared with sunitinib (Sutent) to determine if the combination can improve response rates and outcomes in the frontline setting.

Bradley McGregor, MD, clinical director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, senior physician, instructor in medicine, Harvard Medical School, discusses the goals of the phase III CheckMate-9ER trial, which is evaluating cabozantinib combined with nivolumab in previously untreated patients with advanced or metastatic renal cell carcinoma (RCC).

Bradley McGregor, MD | Authors

Articles

Combination of Cabozantinib/Ipilimumab/Nivolumab Investigated in RCC

CheckMate-9ER Shows Efficacy of Nivolumab/Cabozantinib Combo in RCC

Using Combination Therapy as Treatment of Non-Clear Cell RCC

Atezolizumab and Bevacizumab Studied in Patients With Metastatic RCC

Potential With Cabozantinib Plus Nivolumab in Advanced RCC