Checkpoint inhibitors do not increase likelihood of fast lung cancer progression
Anti-PD-L1 therapy did not appear to be specifically associated with rapid tumor progression compared with chemotherapy among patients with non-small-cell lung cancer, according to an analysis of results from the phase 3 OAK trial presented at European Society for Medical Oncology Immuno-Oncology Congress.
“Hyperprogressive disease, characterized by a rapid increase in tumor growth rate, has been recently reported in patients treated with checkpoint inhibitor monotherapy and requires evaluation of pretreatment tumor growth rates,” David R. Gandara, MD, director of the thoracic oncology program at UC Davis Comprehensive Cancer Center, and colleagues wrote. “Hyperprogressive disease is rare and has been associated with older age, EGFR mutation and poor OS.”
Gandara and colleagues evaluated fast disease progression among patients in the OAK trial who were treated with the anti-PD-L1 monoclonal antibody atezolizumab (Tecentriq, Genentech) or docetaxel in the second- and third-line settings. Researchers defined fast progression as an increase of at least 50% in the sum of the longest diameters (SLD) of tumors from baseline to initial evaluation at 6 weeks, or death due to progressive disease within 12 weeks without a post-treatment scan.
A similar proportion of patients met criteria for fast progression in the atezolizumab (10.4%; n = 44) and docetaxel (9.6%; n = 41) groups. The groups had similar baseline characteristics, although the atezolizumab group included more men (73% vs. 51%) and nonsmokers (20% vs. 10%) and fewer patients who had failed prior treatments (31% vs. 44%).
Among those with baseline indicators for fast progression, investigators assessed OS based on certain baseline characteristics, including early previous treatment failure (31% of atezolizumab group vs. 44% of docetaxel group), lactose dehydrogenase of at least 225 units/mL (55% vs. 51%), SLD of at least 80 mm (48% vs. 44%), and three or more metastatic sites (73% vs. 68%).
Researchers observed superior median OS with atezolizumab vs. docetaxel across all subgroups, including among patients with early prior treatment progression (8.9 months vs. 6.2 months), high lactose dehydrogenase (11 months vs. 8.9 months), high SLD (9.4 months vs. 6.9 months), and three or more metastatic locations (11.7 months vs. 8.6 months).
Because nearly equal proportions of patients in each treatment arm experienced fast progression, these results suggest that suggesting that rapid post-baseline progression is not specific to atezolizumab or anti–PD-L1 therapy in general, according to the researchers.
Additional study is required to understand the underlying biological mechanisms of why certain patients experience tumor growth acceleration, as well as consistent means to measure this phenomenon, especially in the era of combination checkpoint therapies, they added. – by Jennifer Byrne
Gandara DR, et al. Abstract LBA1. Presented at: ESMO Immuno-Oncology Congress; Dec. 13-16, 2018; Geneva.
Disclosures : Gandara reports consultant/advisory roles with AstraZeneca, Genentech and Merck, research funding from Genentech, and parent study support and editorial support funding from F. Hoffman-La Roche. Please see the abstract for all other authors’ relevant financial disclosures.