Drug Combo Bests Sunitinib in RCC

The combination of atezolizumab (Tecentriq; Roche) and bevacizumab (Avastin; Roche) increased progression-free survival (PFS) by up to 3.5 months over sunitinib (Sutent; Pfizer) in patients with metastatic renal cell carcinoma (RCC), according to data presented at the 2018 Genitourinary Cancers Symposium, held February 8–10, in San Francisco, CA.

Several trials are testing or have tested potential alternatives to the multikinase inhibitor sunitinib for RCC. Last year, for example, a phase III trial compared sunitinib to the combination of ipilimumab (Yervoy; Bristol-Meyers Squibb), a CTLA4 inhibitor, and nivolumab (Opdivo; Bristol-Meyers Squibb), which inhibits PD-1. In patients at intermediate or poor risk, whose tumors are likely to progress, the objective response rate (ORR) and progression-free survival (PFS) were higher among those who received the checkpoint inhibitors. In patients whose disease is less likely to progress, however, ORR and PFS were higher in the sunitinib group.

In the phase III IMmotion151 trial, Robert Motzer, MD, of Memorial Sloan Kettering Cancer Center in New York, NY, Brian Rini, MD, of the Cleveland Clinic Taussig Cancer Institute in Ohio, and colleagues tested a different drug combination in 915 patients with untreated advanced or metastatic RCC. The 454 patients in the treatment group received the PD-L1 blocker atezolizumab and the angiogenesis inhibitor bevacizumab; the 461 patients in the control group received sunitinib. The results, which Motzer presented at the symposium, reflect a median follow-up of 15 months.

Atezolizumab and bevacizumab performed better than sunitinib in the 362 patients who were PD-L1–positive. PFS in the group that received the drug combination was 11.2 months, versus 7.7 months in the sunitinib group. The ORR was 43% in the treatment group, versus 35% in the controls.

When the researchers analyzed data from all patients, not just those with PD-L1–positive tumors, they also found an advantage for atezolizumab and bevacizumab. PFS in the patients treated with the combination was 11.2 months, compared with 8.4 months in patients who took sunitinib. In the atezolizumab and bevacizumab group, ORR was 37%, versus 33% in the controls. Overall survival hadn't been reached in either group.

The rate of adverse effects was 40% in patients treated with atezolizumab and bevacizumab and 54% in patients treated with sunitinib. “It's tolerated, and it is an active regimen,” Rini says of the combination.

The researchers acknowledge that their assessment of the results differed from that of an independent committee. Among all patients, the group determined that the PFS for patients who received atezolizumab and bevacizumab was 9.6 months, and 8.3 months in controls. In the PD-L1–positive patients, the committee recorded a PFS of 8.9 months in the patients treated with the combination and 7.2 months in patients who received sunitinib. In the independent assessment, the difference in PFS between the two treatments was not statistically significant. The reason for this discrepancy remains unclear, says Rini. Once the researchers have the overall survival data, however, they will clarify how much benefit the regimen provides, he says.

The study's authors need to explain why their assessment doesn't match that of the independent committee, says Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center in Houston, who wasn't connected to the research. However, he says that, given the data, he would consider prescribing the combination if it's approved. “It might be a reasonable option in favorable-risk patients.”

Rob Jones, MD, of the University of Glasgow in the UK, agrees that the trial supports the combination as a treatment option for certain patients—those with PD-L1–positive tumors. However, he adds, “at the moment there is insufficient evidence to use it for all patients.” –Mitch Leslie