Pooled Biomarker Scores Predicts Ovarian Cancer Survival

Article

Combining three markers of homologous recombination deficiency into a single score may improve treatment decisions for women with ovarian cancer, according to a study reported at the 2016 SGO Annual Meeting.

Combining three markers of homologous recombination deficiency (HRD) into a single score may improve treatment decisions for women with ovarian cancer by predicting those who are likely to benefit from platinum-based chemotherapy, according to a study reported at the 2016 Society of Gynecologic Oncology (SGO) Annual Meeting, held March 19–22in San Diego, California.

Three previously identified HRD markers of genomic instability-telomeric allelic imbalance, large-scale state transitions, and loss of heterozygosity-were combined and tested against each individual biomarker component.

In a retrospective cohort of 859 patients from four studies of platinum-based chemotherapy, the combined score better predicted both progression-free survival (hazard ratio (HR), 0.66; P = 2 × 10-6) and overall survival (HR, 0.55; P = 1 × 10-8 ) compared with each HRD biomarker individually, according to data presented by Gordon B. Mills, MD, PhD, professor of medicine and immunology and chair of systems biology at the University of Texas MD Anderson Cancer Center in Houston (abstract 2).

While each individual component also reached statistical significance in predicting response to a DNA-damaging agent in a univariate analysis of dichotomous scores (low, high), in a bivariate analysis only the combined HRD score reached statistical significance.

The individual HRD biomarkers had a diagnostic accuracy of 85% compared with 90% for the composite HRD score.

In a training cohort of 1,058 patients who were not previously exposed to chemotherapy, a combined HRD score of 42 was determined as an appropriate cut off. Prior studies have shown that many ovarian tumors have defects in homologous recombination, meaning that the tumors are genomically unstable and do not have the mechanisms intact to repair DNA damage. These tumors are more vulnerable to DNA-damaging agents such as platinum-based chemotherapies and PARP inhibitors.

According to Mills, BRCA1 and BRCA2 mutational status plus the HRD combined score is now being assessed as a tool to predict treatment response in several prospective clinical trials for ovarian cancer patients.

Related Videos
Brian Slomovitz, MD, MS, FACOG discusses the use of new antibody drug conjugates for treating patients with various gynecologic cancers.
Developing novel regimens may continue to improve survival outcomes of patients with advanced cervical cancer following the FDA approval of pembrolizumab and chemoradiation, says Jyoti S. Mayadev, MD.
Treatment with pembrolizumab plus chemoradiation appears to be well tolerated with no detriment to quality of life among those with advanced cervical cancer.
Jyoti S. Mayadev, MD, says that pembrolizumab in combination with chemoradiation will be seamlessly incorporated into her institution’s treatment of those with FIGO 2014 stage III to IVA cervical cancer following the regimen’s FDA approval.
Domenica Lorusso, MD, PhD, says that paying attention to the quality of chemoradiotherapy is imperative to feeling confident about the potential addition of pembrolizumab for locally advanced cervical cancer.
Guidelines from the Society of Gynecologic Oncology may help with managing the ongoing chemotherapy shortage in the treatment of patients with gynecologic cancers, according to Brian Slomovitz, MD, MS, FACOG.
Interim data reveal favorable responses in patients with low-grade serous ovarian cancer treated with avutometinib plus defactinib, according to Susana N. Banerjee, MD.
Brian Slomovitz, MD, MS, FACOG, notes that sometimes there is a need to substitute cisplatin for carboplatin, and vice versa, to best manage gynecologic cancers during the chemotherapy shortage.
Findings from the phase 3 MIRASOL trial support mirvetuximab soravtansine as a standard treatment option for platinum-resistant ovarian cancer, according to Ritu Salani, MD.
Trastuzumab deruxtecan appears to elicit ‘impressive’ responses among patients with HER2-positive gynecologic cancers regardless of immunohistochemistry in the phase 2 DESTINY-PanTumor02 trial.
Related Content