An analysis of patient-reported outcomes from the phase II IMmotion150 study in renal cell carcinoma (RCC) patients showed milder disease- and treatment-related symptoms being reported among those receiving atezolizumab, as well as less symptom interference in daily life, compared with patients taking sunitinib. The results of the analysis (abstract 4515) were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.
Diarrhea, fatigue, and other symptoms can limit the use of tyrosine kinase inhibitors, which have been the first-line treatment for RCC over the past decade. The IMMotion150 trial compared sunitinib to atezolizumab alone or in combination with bevacizumab, and found that the combined therapy improved progression-free survival among patients with 1% or more of tumor-infiltrating lymphocytes expressing programmed death ligand 1 (PD-L1), though there was no significant difference in the intention-to-treat population or in PD-L1–negative patients.
“It’s not surprising. You have a favorable side effect profile because you have a significant number of patients who aren't having much, if any, side effects [with immunotherapy]. It’s validating,” Timothy Gilligan, MD, associate professor of medicine and vice chair of education at the Cleveland Clinic Taussig Cancer Institute, told Cancer Network.
Current regimens are more likely to use two immunotherapy drugs in combination, which could lead to more autoimmune complications than what was seen with atezolizumab in this study, noted Gilligan.
Researchers first reported the full results of IMmotion150 at ASCO 2017. In this sub-analysis, researchers analyzed patient-reported outcomes data prior to treatment initiation, and at days 1 and 22 of each treatment cycle. In total, 101 subjects were included in the atezolizumab plus bevacizumab group, 103 received atezolizumab alone, and 101 received sunitinib.
Both combination atezolizumab/bevacizumab and atezolizumab monotherapy showed a reduced risk of deterioration of core symptoms (atezolizumab/bevacizumab: hazard ratio [HR], 0.74; 95% CI, 0.45–1.20 vs atezolizumab alone: HR, 0.39; 95% CI, 0.22–0.71); RCC symptoms (atezolizumab/bevacizumab: HR, 0.60; 95% CI, 0.38–0.94 vs atezolizumab alone: HR, 0.22; 95% CI, 0.12–0.41); symptom interference with daily life (atezolizumab/bevacizumab: HR, 0.70; 95% CI, 0.47–1.04 vs atezolizumab alone: HR, 0.36; 95% CI, 0.22–0.58); fatigue (atezolizumab/bevacizumab: HR, 0.75; 95% CI, 0.53–1.06 vs atezolizumab alone: HR, 0.48; 95% CI, 0.33–0.70); and fatigue-related interference (atezolizumab/bevacizumab: HR, 0.67; 95% CI, 0.46–0.99 vs atezolizumab alone: HR, 0.38; 95% CI, 0.24–0.60).
The differences between sunitinib and atezolizumab were more pronounced than the differences between sunitinib and combined therapy with respect to core symptom severity (least squares mean, -0.47 vs -0.07), RCC symptom severity (-0.64 vs -0.14), and symptom interference (-0.80 vs -0.28). In addition, 16 separate symptom measures were milder in the atezolizumab group compared with the sunitinib group.
“Clinical activity, safety and PRO [patient-reported outcomes] data for atezo[lizumab] support its investigation in adjuvant tx [therapy] of high-risk RCC pts [patients],” the authors concluded.