Primary and secondary pseudo-stability and progression after atezolizumab with and without bevacizumab

Background Atypical tumor response patterns associated with immunotherapies pose significant challenges for assessing treatment response and clinical decision-making. We characterized the epidemiology, clinical impact, and molecular determinants of pseudo-stability/progression after atezolizumab with and without bevacizumab across several histologies. Methods Post hoc individual-level analysis of 2980 patients across eight randomized trials of atezolizumab in non-small cell lung cancer, urothelial carcinoma, renal cell carcinoma (RCC), and hepatocellular carcinoma. Results Analyses of the temporal characteristics of atypical responses revealed two distinct patterns including primary and secondary pseudo-stability/progression. Primary pseudo-stability/progression is characterized by initial disease progression and subsequent regression, which occurs in 7.7%–12.5% of patients according to cancer type. In contrast, secondary progression is characterized by initial disease control with subsequent radiographic progression followed by tumor regression, and this occurs in 4.4%–10.8% of patients according to cancer type. Compared with patients matched by the same initial radiographic response, primary and secondary pseudo-stability/progression could be associated with similar or inferior overall survival outcomes depending on the cancer type and classification of the initial tumor response. Exploratory analyses indicate that clinical factors are not predictive of atypical responses, but pseudo-stability/progression could be associated with distinct genomic alterations including TSC1/2 in RCC. Conclusions Primary and secondary pseudo-stability/progression occur in a non-trivial proportion of patients across cancer types. Outcomes after pseudo-stability/progression are dependent on cancer type and initial response. Uncovering the clinical and molecular features of pseudo-stability/progression subtypes may guide treatment decisions and identify patients who may benefit from continued immunotherapy despite radiographic progression.