The depth of response (DepOR) is a continuous variable that adds another dimension to the assessment of treatment benefit and may better translate to improve long term outcomes in patients receiving systemic therapies.
Higher depth of response was associated with longer progression-free survival and overall survival in patients with metastatic non small cell lung cancer treated with either a tyrosine kinase inhibitor or immunotherapy. DepOR has been shown to be the prognostic factor for survival in patients with advanced renal cell carcinoma treated with targeted therapy.
In the Phase III JAVELIN renal 101 trial (NCT02684006) shown in Figure 1, first-line of avelumab + axitinib significantly improved progression-free survival in patients with advanced renal cell carcinoma, compared with sunitinib.
Figure 1. JAVELIN renal 101 trial
In this presented poster, the authors report on the correlation of progression-free survival with depth of response with early imaging time points in patients enrolled in the JAVELIN renal 101 trial.
In this trial, tumor shrinkage or growth categorized by best percent change in target lesions on imaging obtained up to 7 and 13 weeks from randomization (Table 1) was assessed. Landmark analysis at 7 and 13 weeks was conducted to reduce bias as patient selection was based on outcomes after randomization. Only patients without progressive disease who had not died at or prior to 13 weeks after randomization were included in this landmark analysis.
The authors also performed a Cox multivariable analysis conducted for progression-free survival for patients in the avelumab+axitinib with depth of response as a continuous variable.
Table 1. Baseline demographics of patients with brain metastasis at enrollment
These presented results are based on the first interim analysis, with a minimum follow up of 6 months in all patients. In the avelumab arm more patients achieved a greater depth of response (>=30%) compared with patients in the sunitinib arm (Figure 2). Additionally, figure 3 demonstrates the progression-free survival outcomes according to the best percent change in target lesions in both treatment arms. A greater depth of response was associated with longer progression-free survival. Additionally, in the avelumab+axitinib arm a deeper depth of response was associated with higher 12-month progression-free survival rate (figure 4).
Figure 2. PFS per BICR in patients with brain metastasis at enrollment 
Figure 3. OS in patients with brain metastasis at enrollment
Figure 4. 12-month PFS by best percent tumor change at 13-week landmark
In this study, the authors concluded that a higher proportion of patients achieved a deeper response in the avelumab+axitinb arm compared with the sunitinib arm. A greater depth of response was associated with higher progression-free survival probabilities in both treatment arms at the 13-week landmark. Lastly, greater tumor shrinkage at early imaging time points was associated with longer progression-free survival in this trial.
Presented by: Martin Voss, MD, Medical Oncologist at Memorial Sloan Kettering Cancer Center