Off-label use of checkpoint inhibitor (CPI) monotherapy in PD-L1–negative or unknown recurrent/metastatic head and neck cancer (R/M HNSCC).

Abstract

6025 Background: The KN-048 study established that the CPI pembrolizumab with chemotherapy should be used for PD-L1 negative R/M HNSCC, while CPI monotherapy has limited efficacy (ORR 4%) in PD-L1 negative disease and should be reserved for PD-L1 positive disease. National patterns of PD-L1 testing and PD-L1 guided treatment selection are unknown. We examined PD-L1 testing rates, the use of CPI overall, and the use of CPI monotherapy in PD-L1 negative or unknown R/M HNSCC (“off-label”), and associated factors. Methods: This retrospective analysis included adult patients starting treatment for R/M HNSCC from 2019-2023 in the Flatiron Health electronic health record (EHR)-derived de-identified national database. Demographics, treatment type, and PD-L1 test results were summarized using descriptive statistics. Specifically, first-line therapy was categorized as CPI monotherapy, CPI with chemotherapy, or chemotherapy and/or cetuximab without CPI. “Off-label” use of CPI was defined as single-agent use without concurrent chemotherapy in patients with negative or unknown PD-L1. Factors associated with “off-label” use were identified using multivariable logistic regression analysis. Results: Our cohort included 3,395 patients with median age 66 (IQR 59-73), 65% White, 77% treated in a community setting, 76% with smoking history, 37% HPV positive, and 72% ECOG PS 0-1. Almost half of patients (44%) did not have a recorded PD-L1 test result; of those with known PD-L1 status (n=1886), distribution of combined positive score (CPS) 0, 1-19, and 20 was 19%, 41%, and 40%, respectively. The most common frontline treatment was CPI monotherapy (43%), followed by chemotherapy/cetuximab (33%) and CPI with chemotherapy (25%). CPI monotherapy use was highly prevalent in patients aged ≥75 (54%) and with ECOG PS ≥ 2 (52%). Among the subgroup of PD-L1 negative or unknown patients (n=1831), 37% (678) received CPI monotherapy (“off-label”). Factors associated with “off-label” CPI monotherapy use included ECOG PS ≥ 2 (OR 1.3), age ≥ 75 (OR 1.3), community practice (OR 1.7), and earlier year (HR 1.2) (all p<0.05). Conclusions: Most US patients with R/M HNSCC are now receiving CPI-based therapy in the frontline setting, but PD-L1 testing rates remain suboptimal. Use of CPI monotherapy in PD-L1 negative or unknown HNSCC is common, particularly in elderly patients and those with poor performance status.[Table: see text]