Bradley McGregor, MD, physician, Genitourinary Oncology program, Dana-Farber Cancer Institute, and instructor of medicine, Harvard Medical School, discusses whether patients with renal cell carcinoma (RCC) need frontline combination therapy.

Frontline combination therapies have taken hold of the RCC landscape, but physicians have yet to determine whether everyone should receive a frontline combination therapy, says McGregor. In the CheckMate-214 trial, the combination of ipilimumab (Yervoy) and nivolumab (Opdivo) was compared with sunitinib (Sutent) in the frontline setting and showed an improvement in overall survival. However, patients with good-risk disease demonstrated a higher rate of progression-free survival with sunitinib than with the combination.

Additionally, patients in the trial were accrued prior to the FDA’s approval of the combination in the United States. Less than 30% of patients who received sunitinib crossed over to receive immunotherapy in the trial. Researchers did not allow crossover until the data were reported, which was in 2016. Therefore, it is unknown if patients who receive frontline sunitinib and second-line immunotherapy experience the same magnitude of benefit, explains McGregor.

Videos

Dr. McGregor on Whether Patients Need Frontline Combinations in RCC

Bradley McGregor, MD, physician, Genitourinary Oncology program, Dana-Farber Cancer Institute, instructor of medicine, Harvard Medical School, compares recent data with combination therapy in renal cell carcinoma (RCC).

Results from the phase III CheckMate-214 trial and the IMmotion151 trial have proven the success of combination therapy in patients with advanced RCC.

In April 2018, the FDA approved the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) as a frontline treatment for intermediate- and poor-risk patients with advanced RCC. This approval was based off findings from the phase III CheckMate-214 study, which showed a 32% reduction in the risk of death with the combination compared to sunitinib (Sutent). McGregor says that the most appealing data out of this trial were the complete response (CR) rates, specifically in the PD-L1—positive subgroup, which was 16%. The CR rate for the PD-L1–negative group was comparable with what is seen with interleukin-2, he added.

Findings from the IMmotion151 trial showed that the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) reduced the risk of death by 26% compared with sunitinib in patients with untreated PD-L1—positive metastatic RCC. McGregor says that the most appealing thing about this combination is the toxicity profile. It is a very well-tolerated regimen as opposed to nivolumab plus ipilimumab, where the data suggest the combination is appropriate only for intermediate- and poor-risk patients.

Bradley McGregor, MD, physician, Genitourinary Oncology program, Dana-Farber Cancer Institute, instructor of medicine, Harvard Medical School, compares recent data with combination therapy in renal cell carcinoma.
 

Dr. McGregor Compares Recent Data With Combinations in RCC

Bradley McGregor, MD, physician, Genitourinary Oncology program, Dana-Farber Cancer Institute, instructor of medicine, Harvard Medical School, discusses new combinations with immunotherapy in renal cell carcinoma (RCC).

In addition to the 2 recent phase III trials, CheckMate-214 and IMmotion151, there are emerging combinations with immunotherapy showing promise in RCC. There are currently clinical trials of immunotherapy agents in combination with tyrosine kinase inhibitors, says McGregor. These trials include pembrolizumab (Keytruda) plus lenvatinib (Lenvima), axitinib (Inlyta) plus avelumab (Bavencio), and axitinib plus pembrolizumab.

McGregor says that Dana-Farber Cancer Institute is participating in the CLEAR trial, which is investigating pembrolizumab with lenvatinib versus lenvatinib with everolimus (Afinitor) versus sunitinib (Sutent). Additionally, there is a phase III study of nivolumab (Opdivo) plus cabozantinib (Cabometyx) versus sunitinib in patients with RCC.

Although these regimens have shown benefit in patients with RCC, McGregor cautions that combination therapy comes with increased toxicity. For example, about 60% of patients who take ipilimumab (Yervoy) plus nivolumab require steroids.

Bradley McGregor, MD, physician, Genitourinary Oncology program, Dana-Farber Cancer Institute, instructor of medicine, Harvard Medical School, discusses new combinations with immunotherapy in renal cell carcinoma.

Dr. McGregor on New Combinations With Immunotherapy in RCC

Bradley McGregor, MD, physician, Genitourinary Oncology program, Dana-Farber Cancer Institute, instructor of medicine, Harvard Medical School, discusses combinations of immunotherapy for patients with kidney cancer.

Two phase III trials that are investigating immunotherapy combinations are CheckMate-214 and IMmotion151. CheckMate-214 investigated nivolumab (Opdivo) and ipilimumab (Yervoy), whereas IMmotion151 investigated atezolizumab (Tecentriq) and bevacizumab (Avastin). The CheckMate-214 study saw impressive complete response (CR) rates of 16% for patients with PD-L1 expression.

IMmotion151 also had a CR rate of 9%. The most appealing aspect of that trial was the low toxicity profile. In CheckMate-214, it seemed to only work best for intermediate- and poor-risk patients, says McGregor. But, in the IMmotion151 study, there was a benefit across all subgroups, independent of risk status.

There are multiple ongoing phase III trials inspired by phase I data that showed impressive response rates. The hope is that those response rates translate into the phase III trials and improve CR rates.

Dr. McGregor on Immunotherapy Combinations in Kidney Cancer

Bradley McGregor, MD, physician, Genitourinary Oncology program, Dana-Farber Cancer Institute, instructor of medicine, Harvard Medical School, discusses the future of treatment for renal cell carcinoma (RCC).

Considering recent data with combinations such as axitinib (Inlyta) plus avelumab (Bavencio), and lenvatinib (Lenvima) plus pembrolizumab (Keytruda), McGregor believes that combinations in RCC will be moving toward the frontline setting.

Multiple trials are ongoing to determine what that combination will be.

Bradley McGregor, MD, physician, Genitourinary Oncology program, Dana-Farber Cancer Institute, instructor of medicine, Harvard Medical School, discusses the future of treatment for renal cell carcinoma.
 

Bradley McGregor, MD

Articles

Dr. McGregor on Whether Patients Need Frontline Combinations in RCC

Dr. McGregor Compares Recent Data With Combinations in RCC

Dr. McGregor on New Combinations With Immunotherapy in RCC

Dr. McGregor on Immunotherapy Combinations in Kidney Cancer

Dr. McGregor Discusses the Future of Treatment for RCC