First-line therapy with atezolizumab, an anti–PD-L1 immune checkpoint inhibitor, and bevacizumab, a vascular endothelial growth factor (VEGF)-targeted agent, showed progression-free survival (PFS) benefit compared with sunitinib in patients with PD-L1–positive metastatic renal-cell carcinoma in the phase 2 IMmotion150 and phase 3 IMmotion151 trials.1-3 In IMmotion150, patients with previously untreated, metastatic renal-cell carcinoma were randomly assigned to receive atezolizumab 1200 mg once every 3 weeks, atezolizumab 1200 mg plus bevacizumab 15 mg/kg every 3 weeks, or once-daily sunitinib 50 mg for 4 weeks on and 2 weeks off. The coprimary end points were PFS in the intent-to-treat and PD-L1–positive populations. In the intent-to-treat population, atezolizumab was not associated with improved PFS versus sunitinib as monotherapy (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.82-1.71) or as combination therapy with bevacizumab (HR, 1.0; 95% CI, 0.69-1.45). In the PD-L1–positive population, PFS favored atezolizumab plus bevacizumab versus sunitinib (HR, 0.64; 95% CI, 0.38-1.08).2
In a subsequent phase of IMmotion150, patients whose disease progressed on monotherapy with atezolizumab or sunitinib were eligible for second-line treatment with atezolizumab plus bevacizumab. Efficacy, safety, and biomarker correlates of response in the second phase of IMmotion150 were secondary end points.1
Of the 59 patients in the atezolizumab group and 78 patients in the sunitinib group, 44 and 59 enrolled in the second-line phase of the trial, respectively. The objective response rate (ORR) was 27% (95% CI, 19%-37%), with 1 complete response and 26 partial responses. Among the 16 patients who responded to first-line treatment, the ORR was 44% (95% CI, 20%-70%). In contrast, patients who did not respond in the first-line setting had an ORR of 24% (95% CI, 15%-34%). Among those who responded, the median duration of response was 18.3 months.1
From the start of second-line therapy, the median PFS was 8.7 months (95% CI, 5.6-13.7 months), with 25 patients not having a PFS event at the time of data cutoff.1
PD-L1 status was assessed at progression in 30 patients. Among those with PD-L1–positive tumors at progression, ORR was 42% compared with 22% in those with PD-L1–negative tumors. Median PFS was 10.9 months in patients with PD-L1–positive tumors and 5.8 months in those with PD-L1–negative tumors. In contrast, PD-L1 status at baseline was not associated with efficacy outcomes in the second-line setting.1
A total of 30% of patients had grade 3 or 4 treatment-related adverse events. The most frequently reported treatment-related adverse events were proteinuria (13%) and hypertension (10%). All incidences of rash, pruritus, and hypothyroidism were grade 1 or 2. Discontinuation of either agent as a result of adverse events was reported in 12% of patients.1
According to the investigators, this is the first prospective study evaluating the efficacy and safety of combination therapy with an anti-VEGF and immunotherapy following progression on an immune checkpoint inhibitor or tyrosine kinase inhibitor. In this study, bevacizumab plus atezolizumab were tolerable and had antitumor activity in patients who were previously treated with sunitinib or atezolizumab monotherapy.1
References
- Powles T, Atkins MB, Escudier B, et al. Efficacy and safety of atezolizumab plus bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with metastatic renal cell carcinoma in IMmotion150: a randomized phase 2 clinical trial. Eur Urol. 2021;79:665-673.
- McDermott DF, Huseni MA, Atkins MB, et al. Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nat Med. 2018;24:749-757. Erratum in: Nat Med. 2018;24:1941.
- 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(6_suppl):Abstract 578.