Update Offers New Insight on Atezolizumab/Bevacizumab Benefit in RCC

The combination of frontline atezolizumab and bevacizumab demonstrated superior efficacy compared with sunitinib or atezolizumab monotherapy in patients with advanced renal cell carcinoma.

Michael Atkins, MD

The combination of frontline atezolizumab (Tecentriq) and bevacizumab (Avastin) demonstrated superior efficacy compared with sunitinib (Sutent) or atezolizumab monotherapy in patients with advanced renal cell carcinoma (RCC), according to findings from the phase II IMmotion150 study

The latest results from the study, which were presented at the 2017 ASCO Annual Meeting, showed that the combination was active in patients on the trial who were initially randomized to sunitinib or atezolizumab monotherapy who crossed over to the combination after progression.

The overall response rate (ORR) among all 95 crossover patients was 26%. The ORR for patients who crossed over to the atezolizumab/bevacizumab combination following progression on sunitinib (n = 54) was 28%, and 24% for those who progressed on atezolizumab (n = 41). At the time of the analysis, 72% of the responses were ongoing. The median duration of response was not yet estimable.

Researchers initially presented results from the IMmotion150 study at the 2017 ASCO Genitourinary Cancers Symposium, and biomarker results were presented at the 2017 AACR Annual Meeting.

The study randomized 305 treatment-naïve patients with locally advanced or metastatic RCC in a 1:1:1 ratio to single-agent atezolizumab at 1200 mg IV every 3 weeks, the same atezolizumab regimen combined with 15 mg/kg IV of bevacizumab every 3 weeks, or single-agent sunitinib at 50 mg orally every day for 4 weeks on, 2 weeks off. PD-L1 positivity was defined as expression of PD-L1 on ≥1% of tumor-infiltrating immune cells.

Among PD-L1—positive patients, the combination reduced the risk of disease progression or death by 36% versus sunitinib (HR, 0.64; 95% CI, 0.38-1.08; P = .095). The median PFS was 14.7 months versus 7.8 months, respectively. The median PFS in the single-agent atezolizumab arm was 5.5 months. The ORRs were 46%, 28%, and 27%, for the combination, atezolizumab, and sunitinib arms, respectively.

In his ASCO presentation, Michael B. Atkins, MD, deputy director of the Georgetown-Lombardi Comprehensive Cancer Center, focused on results from patients who started on monotherapy with either atezolizumab or sunitinib before crossing over to the atezolizumab/bevacizumab combination.

Roughly 75% of patients assigned to monotherapy crossed over. Thirty patients elected to undergo an optional biopsy prior to starting combination treatment.

“This data compares favorably to the first-line response rate for these patients,” Atkins said. “Efficacy parameters appeared to be better with combination in the crossover setting than what was observed in those same patients in the front line.”

Atkins said that the patients who had a brief response to first-line monotherapy had superior response rates overall (39% vs 24%). That was also true in both patients who crossed over following monotherapy with atezolizumab (33% vs 24%) and sunitinib (40% vs 25%).

In the crossover population, the median PFS was 8.8 months overall (range, 5.6-13.7), 8.3 months (range, 3.1-11.2) for patients who crossed over from sunitinib, and 12.6 months (range, 6.0-17.7) for those who crossed over from atezolizumab.

“As with response, median PFS was longer in those who had transient response to front-line monotherapy,” Atkins said. Overall, median PFS was 7.6 months (range, 4.2-12.6) for non-responders compared with 20.1 months (range, 11.2-20.1) for patients who responded to first-line treatment.

In the overall crossover population, investigators found that patients whose tumors had ≥1% PD-L1 expression at baseline had slightly superior response rates, 28% versus 20%. The same held true for patients whose biopsies were positive for PD-L1 expression, 33% versus 22%.

“There was no apparent difference in PFS in the crossover population based on PD-L1 expression in either the baseline or in the progression biopsy,” Atkins said.

Overall, 80% of patients in the crossover population experienced treatment-related adverse events (AEs) of any grade and 29% experienced grade 3/4 treatment-related AEs. There were no AEs that resulted in death. Treatment-related AEs caused 7% of patients to withdrawal.

Atkins said there was “no discernable difference” in safety profile for patients treated with the atezolizumab/bevacizumab combination in the frontline compared with patients treated with the combination in the crossover setting.

“Atezolizumab plus bevacizumab resulted in encouraging efficacy versus first-line sunitinib in PD-L1—positive kidney cancer patients,” he concluded. “Clinical activity was also seen in the atezolizumab and bevacizumab patients regardless of prior first-line monotherapy or first-line response, further supporting combination treatment.”

The ongoing phase III IMmotion151 trial is comparing frontline atezolizumab/bevacizumab with sunitinib in patients with advanced RCC (NCT02420821).

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. 35, 2017 (suppl; abstr 4505).