Response to Abemaciclib and Immunotherapy Rechallenge with Nivolumab and Ipilimumab in a Heavily Pretreated TMB-H Metastatic Squamous Cell Lung Cancer with CDKN2A Mutation, PIK3CA Amplification and TPS 80%: A Case Report

• Type of Material: Article
• Authors: Douglas Dias E Silva, Hospital Israelita Albert Einstein; Guilherme Bes Borba, Hospital Israelita Albert Einstein; Juliana R Beal, Hospital Israelita Albert Einstein; Gehan Botrus, Emory University; Akemi Osawa, Hospital Israelita Albert Einstein; Sérgio Eduardo Alonso Araujo, Hospital Israelita Albert Einstein; Fernando Moura, Hospital Israelita Albert Einstein; Rafael Aliosha Kaliks Guendelmann, Hospital Israelita Albert Einstein; Pedro Luiz Serrano Uson Junior, Hospital Israelita Albert Einstein
• Language: English
• Date: 2023-02-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/ijms24044209
• Title of Journal or Parent Work: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• Volume: 24
• Issue: 4
• Grant/Funding Information: This research received no external funding.
• Keywords: TMB-high; checkpoint inhibition therapy; Life Sciences & Biomedicine; Chemistry, Multidisciplinary; Biochemistry & Molecular Biology; abemaciclib; nivolumab; lung cancer; squamous cell lung cancer; INHIBITOR; Physical Sciences; Science & Technology; PALBOCICLIB; ipilimumab; CYCLE; Chemistry; PATHWAY
• Research Categories: Health Sciences, Oncology

Abstract

Inactivation of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene is considerably more frequent in squamous cell lung cancer (SqCLC) than in other subtypes of lung cancer and may be a promising target for this histology. Here, we present the course of diagnosis and treatment of a patient with advanced SqCLC, harboring not only CDKN2A mutation but also PIK3CA amplification, Tumor Mutational Burden-High (>10 mutations/megabase), and a Tumor Proportion Score of 80%. After disease progression on multiple lines of chemotherapy and immunotherapy, he responded favorably to treatment with the CDK4/6i Abemaciclib and later achieved a durable partial response to immunotherapy rechallenge with a combination of anti-PD-1 and anti-CTLA-4, nivolumab, and ipilimumab.