“The first-line landscape hasn’t changed in the last 7 years, but it is likely to change soon,” said Dr Agarwal, adding that little at the 2017 American Society of Clinical Oncology (ASCO) meeting was likely to be practice-changing.
“I am particularly interested in results from IMmotion150 [Clinicaltrials.gov Identifier: NCT01984242], which is an ongoing phase 2 trial examining the combination of…bevacizumab with…atezolizumab.1
“In patients expressing PD-L1 on their tumors treated with bevacizumab and atezolizumab, PFS [progression-free survival] is 14.7 months compared with 7.8 months with the standard first-line treatment, sunitinib, alone. Bevacizumab and atezolizumab is a rational and novel combination, and this improvement in PFS has never been shown in the first line therapy setting with any other drug or combination yet.
“I am especially anticipating biomarker-based analyses of [IMmotion150],” said Dr Agarwal. “In immunotherapy, a lag time exists between the onset of treatment and the onset of responses. Combining immunotherapy with targeted therapy can potentially overcome this lag time. A hallmark of emergent therapy in first-line treatment is the combination of immunotherapy with targeted treatment,” he added.
Dr Agarwal noted that trials and therapies in the second- and third-line treatment landscapes are evolving rapidly: “over the previous 1.5 years, second- and third-line treatment has undergone a paradigm shift. CheckMate 9ER [Clinicaltrials.gov Identifier: NCT03141177] harbors the potential to take the current paradigm to the next level. This trial combines 2 checkpoint inhibitors (ipilimumab and nivolumab) with cabozantinib and is intended to improve the fraction of durable complete responders.”
New treatment options and novel combinations are also anticipated. “We are going to see a revolution in the number of treatment options for these patients; we will see a variety of treatment options and combinations,” said Dr Agarwal. “The big question is which patients should be given a drug or combination.”
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Dr Vaishampayan added that “there is a novel interleukin-2 immunotherapy that has very specific receptor targeting. It does not cause a lot of the significant side effects and toxicities of earlier IL-2 therapy. Preliminary updates of this and other novel therapies will be on my radar.
“We need to now look to the pipeline to determine what else can be done to make progress.”
- Atkins MB, McDermott DF, Powles T, et al. IMmotion150: A phase II trial in untreated metastatic renal cell carcinoma (mRCC) patients (pts) of atezolizumab (atezo) and bevacizumab (bev) vs and following atezo or sunitinib (sun). J Clin Oncol. 2017;35(suppl; abstr 4505).