Pembrolizumab activity in patients with Fanconi anemia repair pathway competent and deficient tumors

• Published in: Biomarker research 2022-06, Vol.10 (1), p.39-39, Article 39
• Main Authors: Villalona-Calero, Miguel A, Diaz, John P, Duan, Wenrui, Diaz, Zuanel, Schroeder, Eric D, Aparo, Santiago, Gatcliffe, Troy, Albrecht, Federico, Venkatappa, Siddhartha, Guardiola, Victor, Garrido, Sara, Rubens, Muni, DeZarraga, Fernando, Vuong, Hao
• Format: Article
• Language: English
• Subjects: Analysis; Anemia; Antitumor activity; Biomarkers; Cancer; Cancer therapies; Care and treatment; Chemotherapy; Colorectal cancer; Development and progression; DNA repair; Drug approval; Endometrial cancer; Endometrium; FancD2; Fanconi; Fanconi syndrome; Fanconi's anemia; FDA approval; Genomics; Homologous recombination; Hypotheses; Immune checkpoint inhibitor; Metastasis; Microbiomes; Mutation; Patients; Pembrolizumab; Population studies; Tumors
• ISSN: 2050-7771; 2050-7771
• DOI: 10.1186/s40364-022-00386-0

Given the observed antitumor activity of immune-checkpoint-inhibitors in patients with mismatch-repair deficient (MSI-H) tumors, we hypothesized that deficiency in homologous-recombination-repair (HRR) can also influence susceptibility. Patients with disease progression on standard of care and for whom pembrolizumab had no FDA approved indication received pembrolizumab. Patients with MSI-H tumors were excluded. Objectives included immune-related objective response rate (iORR), progression-free survival (PFS) and 20-weeks-PFS. Pembrolizumab was given every 3 weeks and scans performed every six. We evaluated a triple-stain (FANCD2foci/DAPI/Ki67) functional assay of the Fanconi Anemia (FA) pathway: FATSI, in treated patients' archived tumors. The two-stage sample size of 20/39 patients evaluated an expected iORR≥20% in the whole population vs. the null hypothesis of an iORR≤5%, based on an assumed iORR≥40% in patients with functional FA deficiency, and