Biotechnology

HRD detection predicts sensitivity to platinum-based chemotherapy for

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Homologous Recombination Deficiency (HRD) is a biomarker that predicts treatment of ovarian cancer with PARP inhibitors or treatment of breast cancer with first-line platinum-based chemotherapy. However, limited research is documented on the prediction of platinum-based treatment with HRD as a biomarker in ovarian cancer patients, especially in the Chinese population.

Homologous Recombination Deficiency (HRD) is a biomarker that predicts treatment of ovarian cancer with PARP inhibitors or treatment of breast cancer with first-line platinum-based chemotherapy. However, limited research is documented on the prediction of platinum-based treatment with HRD as a biomarker in ovarian cancer patients, especially in the Chinese population.

This first prospective Chinese cohort study, co-conducted by BGI Genomics clinical investigator Dr. Shao Di and Fudan University Shanghai Cancer Center team and published in Journal of Ovary Research demonstrated that HRD testing can accurately predict the sensitivity of platinum-based chemotherapy for ovarian cancer patients.

Research methods

This study included 240 patients with primary treatment of serious high-grade ovarian cancer (HGSOC) who were admitted to Fudan University Cancer Hospital from the interval from January 2016 to September 2018. The patients received more than two cycles of platinum-containing adjuvant chemotherapy after surgery and were classified as platinum- sensitive (Pt) and platinum-resistant according to the time of ovarian cancer recurrence.

All patients were tested by screening gene panel test for 68 HRR genes, to assess the mutation status of HRR-associated genes such as BRCA. Of these, 118 samples underwent HRD testing to assess loss of heterozygosity (LOH), telomere allele disequilibrium (TAI), and large segmental recombination disorder (LST) status. The Kaplan-Meier method was used to plot survival curves and the effectiveness of this test in predicting patient outcomes.

Results

Of the 240 HGSOC patients enrolled in this study, 82.5% had Pt-sensitive cancer with a platinum-free interval of more than six months. The study showed that 31.2% of patients had BRCA gene mutations, 53 in BRCA1 and 22 in BRCA2 (Figure 1). In addition, 25% of patients have mutations in the non-BRCA/HRR gene.

The proportion of patients with positive HRD status was 64.4%. The results revealed that, compared with the Western population, a higher proportion of Chinese ovarian cancer patients benefited from PARP inhibitor maintenance therapy.

HRR gene mutations and HRD status is highly correlated with sensitivity to platinum chemotherapy in patients with HGSOC.

The findings indicated that the HRD scores of patients sensitive to platinum treatment were slightly higher than those of Pt-resistant patients (Fig. 2A).

Further analysis also found that the levels of Pt-sensitive patients in the HRD+ BRCAwt and HRD+ BRCAwt groups were significantly higher than those in the HRD-BRCAwt group (Fig. 2B).

Similarly, this study also found that Pt-sensitive patients were more enriched in the BRCA mutation group and the HRR non-BRCA mutation group than the HRR wt group.

The analysis showed that patients with positive HRD status had significantly longer progression-free survival (PFS) compared to patients with negative HRD status. (mean PFS: 30.5 months vs 16.8 months, p=0.001 – Fig.3A).

Conclusion

This study shows for the first time that HRD is a valid biomarker tool for predicting sensitivity to platinum-based chemotherapy in Chinese ovarian cancer patients in an unselected prospective cohort.

Learning also found a higher HRD positivity rate in Chinese ovarian cancer patients than in the Western populationdemonstrated that HRD testing could screen a higher proportion of the Chinese PARP-inhibiting population to facilitate precision therapy.

About BGI Genomics

BGI Genomics, headquartered in Shenzhen China, is the world’s leading provider of integrated precision medicine solutions. Our services cover more than 100 countries and regions, involving more than 2,300 medical institutions. In July 2017, as a subsidiary of BGI Group, BGI Genomics (300676.SZ) was officially listed on the Shenzhen Stock Exchange.


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