Comparison of fast-progression, hyperprogressive disease, and early deaths in advanced non-small-cell lung cancer treated with PD-1/PD-L1 inhibitors or chemotherapy

Roberto Ferrara, Laura Mezquita, Matthieu Texier, Jihene Lahmar, Clarisse Audigier-Valette, Laurent Tessonnier, Julien Mazieres, Gerard Zalcman, Solenn Brosseau, Sylvestre Le Moulec, Laura Leroy, Boris Duchemann, Corentin Lefebvre, Remi Veillon, Virginie Westeel, Serge Koscielny, Stephane Champiat, Charles Ferté, David Planchard, Jordi RemonMarie Eve Boucher, Anas Gazzah, Julien Adam, Giuseppe Lo Russo, Diego Signorelli, Marina Chiara Garassino, Jean Charles Soria, Caroline Caramella, Benjamin Besse

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    Abstract

    PURPOSE Hyperprogressive disease (HPD), fast progression (FP), and early death (ED) have been described in 13.8%, 4.7%, and 5.6% and in 5.1%, 2.8%, and 6.8%, respectively, of patients with non-small-cell lung cancer (NSCLC) treated with single-agent programmed cell death ligand 1 inhibitors (ICI) or chemotherapy, respectively. Whether FP/ED and HPD represent overlapping patterns is unknown. PATIENTS AND METHODS FP, ED, and HPD were retrospectively assessed in patients with NSCLC treated with single-agent ICI or chemotherapy. Eligibility required 2 computed tomography (CT) scans before and 1 CT scan during treatment. (1) HPD, (2) FP, (3) ED were defined as (1) RECIST version 1.1 progression at first CT scan and tumor growth rate variation per month > 50%, (2) ≥ 50% increase in the sum of the longest diameters of target lesions within 6 weeks from baseline, and (3) death as a result of radiologic progression within 12 weeks from baseline CT scan, respectively. RESULTS Of 406 ICI-treated NSCLC, 56 patients (13.8%), 9 patients (2.2%), and 36 patients (8.8%) were HPD, FP, and ED, respectively. Eight (14.2%) and 20 (35.7%) of 56 patients with HPD were also FP and ED. ED significantly correlated with baseline Eastern Cooperative Oncology Group performance status ≥ 2 compared with HPD (33% v 13%, P = .02). Overall survival was significantly longer for HPD (3.4 months [95% CI, 2.7 to 4.0 months]) compared with FP (0.7 months [95% CI, 0.6 to 0.8 months]); HR, 0.18 [95% CI, 0.08 to 0.42]; P < .0001) and ED (1.4 months [95% CI, 1.3 to 1.6 months]); HR, 0.19 [95% CI, 0.11 to 0.34]); P < .0001), whereas it did not differ between FP and ED (HR, 1.3 [95% CI, 0.56 to 3.0]; P = .55). Of 59 patients with NSCLC treated with single-agent chemotherapy, the HPD, FP, and ED rates were 5.1%, 1.7%, and 6.7%, respectively. CONCLUSION FP, ED, and HPD represent distinct progression patterns with limited overlap and different survival outcomes.

    Original languageEnglish
    Pages (from-to)829-840
    Number of pages12
    JournalJCO Precision Oncology
    Volume4
    DOIs
    Publication statusPublished - 1 Jan 2020

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