Tumor mutation burden (TMB), BRCA1/2 mutations, and homologous DNA repair deficiency (HRD) are not associated with immune checkpoint inhibitor response or survival in recurrent ovarian cancer, according to an original report published in JCO Precision Oncology (online June 16, 2020; doi:10.1200/PO.20.00069).
HRD ovarian cancers—including those with BRCA1/2 mutations—tend to have higher levels of genetic instability that can result in higher immunogenicity. These tumors have been suggested to respond better to immune checkpoint inhibitors than homologous DNA repair-proficient ovarian cancers. However, further data is needed to confirm this belief.
Dmitriy Zamarin, MD, PhD, department of medicine, Gynecologic Medical Oncology Service, Memorial Sloan Kettering Cancer Center (New York, NY), and colleagues evaluated the associations between BRCA1/2 mutations, HRD, and other genomic parameters with response to immune checkpoint inhibitors and survival in ovarian cancer. The retrospective analysis considered 143 patients with recurrent disease who were treated with immune checkpoint inhibitors.
Immune checkpoint inhibitor response was predefined as lack of disease progression for at least 24 weeks. Researchers determined associations of BRCA1/2 status and genomic alterations with progression-free survival (PFS) and overall survival (OS) through Cox proportional hazards models.
Dr Zamarin and colleagues noted that 134 of the patients had known BRCA1/2 mutation status. Deleterious germline or somatic BRCA1/2 mutations were present in 24% (n = 31) of patients. No association between presence of BRCA1/2 mutations and response (P = .796) or survival was found.
Additionally, genomic analysis of 73 patients yielded no association between TMB (P = .344) or HRD (P = .222) with response, PFS, or OS.
Furthermore, there was no significant differences in somatic gene alterations between responders and non-responders. However, high fraction of genome altered was associated with an improvement in PFS (P = .014) and OS (P = .01).
In their concluding remarks, authors of the study cautioned against the use of TMB, BRCA1/2, and HRD as selection criteria for immune checkpoint inhibitors in recurrent ovarian cancer. “Fraction of genome altered should be investigated further as a biomarker of response to immunotherapy in ovarian cancer,” they added.—Zachary Bessette
