Expert Discusses Atezolizumab/Bevacizumab Data in RCC

Brian Rini, MD

Brian Rini, MD

Atezolizumab with bevacizumab could prove to be a practice-changing combination regimen in the frontline treatment of kidney cancer, according to Brian I. Rini, MD.

Data from the IMmotion 151 trial showed that the combination compared with sunitinib (Sutent) decreased disease progression or death by 26% for patients with previously untreated PD-L1—positive metastatic renal cell carcinoma.¹

Median progression-free survival (PFS) for those with PD-L1 expression on >1% of immune cells (n = 362) was a coprimary endpoint of the study along with overall survival (OS). Results showed that there was a 3.5-month improvement in median PFS at 11.2 months with atezolizumab/bevacizumab and 7.7 months with sunitinib (HR, 0.74; 95% CI, 0.57-0.96;P= .0217).

In the study, 915 patients were randomized to receive atezolizumab plus bevacizumab (n = 454) and sunitinib (n = 461). Atezolizumab was administered at 1200 mg and bevacizumab was given at 15 mg/kg every 3 weeks. Sunitinib was given orally at 50 mg/day for 4 weeks, followed by a 2-week rest period.

Patient-reported outcomes (PROs) from this study were presented at the 2018 ASCO Annual Meeting.²Findings showed that baseline completion in the intent-to-treat (ITT) population was >80% and >70% until week 57 of the study. Post-baseline visits showed milder and stable symptom severity for those who received atezolizumab and bevacizumab versus sunitinib. Rini added that a greater proportion of patients on the combination reported little to no issue from a toxicity perspective compared with those on sunitinib.

In an interview withTargeted Oncology, Rini, a professor of medicine at Cleveland Clinic, discussed atezolizumab/bevacizumab as an effective frontline combination in RCC, as well as PROs with the regimen.

TARGETED ONCOLOGY:Can you give some background on the IMmotion 151 trial?

Rini:IMmotion 151 was a randomized phase III trial that took previously untreated patients with metastatic cancer and randomized them to a combination of atezolizumab and bevacizumab. We wanted to prove a PFS advantage in patients who were PD-L1 positive; that was the primary endpoint of the trial.

It showed about a 3-month to 3.5-month advantage in the medians to that. The coprimary endpoint was OS in the ITT population. That data were relatively immature; only about 30% of events trended toward favoring atezolizumab/bevacizumab, both in ITT and PD-L1—positive subgroups. Therefore, it looks like clinically, there is activity to the combination. Another one of the coprimary endpoints was PROs.

TARGETED ONCOLOGY:What are the data presented with the PROs?

Rini:At the 2018 ASCO Annual Meeting, the authors presented a separate abstract on PROs, which was a secondary endpoint, and there were various measures of PROs that were used. One of the distinguishing features of this regimen was tolerability. As you may know, there are a number of immune-base combinations that are coming out for kidney cancer. Atezolizumab/bevacizumab and a number of others are in large phase III trials. We don’t yet have efficacy results to know if there are some differences in efficacy, but there were will be some with tolerability.

One of the great things about atezolizumab/bevacizumab is that it’s really well tolerated. In short, that's what the abstract is about: these various measures. The average time to deterioration as measured by this certain PRO was about 11 months in the atezolizumab/bevacizumab arms. It was about 4 months in the other arm. This was striking because it means patients aren’t worse under atezolizumab/bevacizumab until their disease gets worse. Toxicity isn’t an issue.

TARGETED ONCOLOGY:Why is there such a synergy between atezolizumab and bevacizumab?

Rini:One [reason] is the clinical rationale. They're both active as monotherapy and oncologists like to stick drugs together, so essentially, A plus B. This creates a favorable immune environment for the immuno-oncology agent to act. With some of these emerging data with these combos; it’s clear there is some substantial activity.

TARGETED ONCOLOGY:There is talk about a potential FDA approval for this combination. How would that shake up the kidney cancer landscape?

Rini:It would be one of, what I think, will be a string of combination approvals with maybe 3 or 4 others to follow. It would change the standard of care in kidney cancer treatment; there's no question about it. The current treatment has been in place for decades. In a few years, not many patients will be getting monotherapy.

TARGETED ONCOLOGY:What else about the PRO findings from the IMmotion 151 abstract is important for people to understand?

Rini:It is important that there are several different scales done. I don’t think anyone knows what the perfect PRO measure is. Looking at it in different ways gives you a better chance to understand the regimen. It boils down to how well tolerated the drugs are. It's a ratio of benefit to risk.

References:

1. Motzer RJ, Powles T, Atkins MB, et al. IMmotion151: a randomized phase iii study of atezolizumab plus bevacizumab vs sunitinib in untreated metastatic renal cell carcinoma (mRCC).J Clin Oncol.2018;36 (suppl 6S; abstr 578).
2. Escudier, B. Motzer, R. Rini, B. Patient-reported outcomes (PROs) in IMmotion151: Atezolizumab (atezo) + bevacizumab (bev) vs sunitinib (sun) in treatment (tx) naive metastatic renal cell carcinoma (mRCC).