Abstract
BackgroundDespite the wide-spread use of immune checkpoint inhibitors (ICIs) in cancer chemotherapy, reports on patients developing acquired resistance (AR) to ICI therapy are scarce. Therefore, we first investigated the characteristics associated with shorter durable responses of ICI treatment and revealed the clinical patterns of AR and prognosis of the patients involved.MethodsWe conducted a retrospective multi-center cohort study that included NSCLC patients with PD-L1 tumor proportion scores of ≥50% who received first-line pembrolizumab and showed response to the therapy. Among patients showing response, progression-free survival (PFS) was investigated based on different clinically relevant factors. AR was defined as disease progression after partial or complete response based on Response Evaluation Criteria in Solid Tumors. Among patients with AR, patterns of AR and post-progression survival (PPS) were investigated. Oligoprogression was defined as disease progression in up to 5 individual progressive lesions.ResultsAmong 174 patients who received first-line pembrolizumab, 88 showed response and were included in the study. Among these patients, 46 (52%) developed AR. Patients with old age, poor performance status (PS), at least 3 metastatic organs, or bone metastasis showed significantly shorter PFS. Among 46 patients with AR, 32 (70%) developed AR as oligoprogression and showed significantly longer PPS than those with non-oligoprogressive AR.ConclusionsPatients with old age, poor PS, at least 3 metastatic organs, or bone metastasis showed shorter durable responses to pembrolizumab monotherapy. Oligoprogressive AR was relatively common and associated with better prognosis. Further research is required to develop optimal approaches for the treatment of these patients.
Highlights
Despite the wide-spread use of immune checkpoint inhibitors (ICIs) in cancer chemotherapy, reports on patients developing acquired resistance (AR) to Immune checkpoint inhibitor (ICI) therapy are scarce
Study population We conducted a retrospective cohort study including patients with advanced Non-small cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) of ≥50%, who received pembrolizumab as a firstline therapy between February 1, 2017 and April 31, 2018, and had initial response to it at any of the 11 participating institutions belonging to Hanshin Oncology clinical Problem Evaluation (HOPE) group
AR was defined as disease progression after partial response (PR) or complete response (CR) to pembrolizumab therapy based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1
Summary
Despite the wide-spread use of immune checkpoint inhibitors (ICIs) in cancer chemotherapy, reports on patients developing acquired resistance (AR) to ICI therapy are scarce. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancer cases, and the majority of these are diagnosed at an advanced stage [2, 3]. Immune checkpoint inhibitors (ICIs) have been established as a therapy regimen for several types of malignancies, including advanced NSCL C. Pembrolizumab, a fully humanized monoclonal antiprogrammed cell death 1 (PD-1) antibody, showed better treatment outcomes than platinum-based chemotherapy for previously untreated advanced NSCLC with positive programmed cell death ligand 1 (PD-L1) status [4, 5]. Especially better treatment outcomes were observed for patients with PD-L1 tumor proportion score (TPS) ≥50%. Pembrolizumab monotherapy has become a standard first-line treatment, for patients with PD-L1 TPS of ≥50%
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