Outcomes of responders to PD-1/PD-L1 inhibitors who discontinue therapy after sustained disease control

• Type of Material: Article
• Authors: Harsh Sharma, University of New Mexico, Albuquerque; Krishna R Moturi, University of New Mexico, Albuquerque; Vernon S Pankratz, University of New Mexico, Albuquerque; Emrullah Yilmaz, Cleveland Clinic; Olumide Gbolahan, Emory University; Atul Kumar, University of New Mexico, Albuquerque; Neda Hashemi-Sadraei, University of New Mexico, Albuquerque
• Language: English
• Date: 2023-04-28
• Publisher: Springer (part of Springer Nature)
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
• Final Published Version (URL): http://dx.doi.org/10.1007/s00432-023-04812-0
• Title of Journal or Parent Work: JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
• Start Page: 1
• End Page: 8
• Grant/Funding Information: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
• Keywords: Patient response; PD-L1; Cancer immunology; Immunotherapy; Immune checkpoint; PD-1
• Research Categories: Health Sciences, Oncology

Abstract

Background PD-1/PD-L1 immune checkpoint inhibitors (ICIs) are widely used in the treatment of metastatic malignancies. Judiciously balancing disease control (DC) against development of immune-related adverse events (irAE) remains a crucial aspect of treatment. The effect of treatment discontinuation after sustained disease control (SDC) is unknown. The purpose of this analysis was to evaluate outcomes of responders to ICI who discontinue treatment after a minimum of 12 months (SDC). Methods We retrospectively reviewed the database of the University of New Mexico Comprehensive Cancer Center (UNMCCC) between 2014 and 2021 and identified patients who had received ICI. Patients with metastatic solid tumors who had stopped ICI therapy after achieving SDC [stable disease, partial response, complete response (SD, PR, CR)] were selected and outcomes reviewed from their electronic health records. Results We identified 204 patients who were treated with ICI for various solid cancers. Forty-four patients (21.6%) met the criteria, of whom 35 with follow-up data were included in the final analysis; including 11 melanoma, 5 non-small cell lung, 4 head & neck, 8 renal, 4 urothelial, 1 anal, 1 Merkel cell carcinoma, and 1 liposarcoma. Patients were divided into two groups: those who stopped ICI due to an irAE [irAE group, n = 14, median treatment time (MTT), 16.6 mo] and those who stopped due to other reasons (eg completion of 2 years of therapy, n = 20, non-cancer related surgery, n = 1) (non-irAE group, n = 21, MTT, 23.7 mo). Among the irAE group, the most common irAE included pneumonitis, rash, transaminitis, and fatigue. As of data cutoff date, 9 of 14 (64%) patients continued to show SDC. Only 5 of 14 (36%) patients in this group experienced progression of disease (PD), with 1 of 2 patients achieving DC (median follow-up of 19.2 mo after last dose of treatment, range 3–50.2 mo). Among the non-irAE group, 13 of 21 (62%) continued to have SDC. Eight of 21 (38%) experienced PD after stopping treatment, 7 of whom received ICI rechallenge, with 2 of 7 achieving DC (median follow-up of 22.2 mo, range 3.6-54.8 mo). At a median follow-up of 21.3 mo from stopping ICI therapy (range, 3–54.8 mo), 10 patients (71%) from the irAE group and 13 (61.9%) from the non-irAE group are in DC and have not experienced PD. Conclusions We demonstrate that 22 (66%) patients experienced SDC, regardless of cancer type or development of irAE. After including patients who were re-challenged with ICI due to PD, 25 (71%) remain in DC. Future prospective malignancy-specific trials are warranted to evaluate optimal treatment duration.