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Precision Medicine: A New Era for Ovarian Cancer

Holman, Laura L. MD, MS

doi: 10.1097/01.COT.0000525218.72486.f4
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ovarian cancer; precision medicine

ovarian cancer; precision medicine

We've come a long way in treating ovarian cancer. This treatment has historically consisted of debulking surgery for nearly every patient, but it is evolving to become more informed and precise. Diagnostic laparoscopy, for example, can be used to distinguish those who may benefit from primary surgery and those who may respond better to neoadjuvant chemotherapy.

With recent advances in technology and a deeper understanding of the underlying biology, we may have the opportunity to go even further. Today, developments in DNA sequencing have brought comprehensive genomic profiling (CGP) to the forefront of cancer treatment, and they are helping us bring the promise of precision oncology to ovarian cancer.

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Learning More Through Genomics

Genomic profiling has allowed us to identify molecular alterations or genomic markers of disease. For example, our understanding of the BRCA genes in ovarian cancer has led to the development of targeted therapies that are effective in patients specifically with BRCA mutations. CGP, which often probes hundreds of different cancer-related genes, provides an unprecedented look into each patient's specific cancer.

This has tremendous value toward identifying subtypes of disease and guiding the development of new medicines. Just as importantly, this could help physicians determine who is most likely to benefit from a specific treatment and who is not likely to respond.

This ability to both match appropriate treatments and forgo ineffective ones could significantly improve overall outcomes as well as quality of life. It also opens up the possibility for alternative treatments or enrollment in clinical trials.

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Predicting First-Line Response

As one piece of evidence demonstrating this potential value, my colleagues and I recently presented data at the Society of Gynecologic Oncology's 2017 Annual Meeting on Women's Cancer on the ability of CGP to identify patients who may respond better to first-line chemotherapy (Poster Session 186).

In a study of 54 ovarian cancer patients who underwent CGP, we found that 63 percent of patients had a clinically-relevant genomic alteration, defined as those associated with a targeted therapy. These were most commonly in PIK3CA, KRAS, and ARID1A.

In addition, we also found that, among patients with high-grade serous histology, individuals with a progression-free survival (PFS) of >15 months had a larger number of DNA segments than patients who survived ≤ 14 months. These findings indicate that longer PFS may be associated with a more fractured tumor genome (see Fig. 1).

Most exciting about these data is that they suggest the presence of genomic alterations associated with survival and that may predict the length of time before ovarian cancer recurs (Fig. 2).

While this study was limited due to its retrospective nature and small sample size, we believe these findings are an important step in driving continued research into these genomic alterations. Larger studies may identify additional genomic patterns associated with survival. Ultimately, a better understanding of these associations will allow us to stratify patients into risk categories and direct treatment more effectively.

Fig. 1

Fig. 1

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Path to Personalized Care

Historically, ovarian cancers were classified by their appearance under the microscope and CGP was not broadly employed as a tool for clinical decision-making. In our practice, we had typically reserved this testing for patients who had recurred or for those whose cancer has a very rare histology.

However, the growing amount of data are promising, and continuing research into the genomics of ovarian cancer may one day reveal predictive biomarkers of response or new drug targets.

Fig. 2

Fig. 2

For example, in just the past 3 years, three new drugs have been approved specifically for ovarian cancer and the response rates are impacted by the molecular features of the individual patient's tumor. But even in light of this progress, I believe we're only at the tip of the iceberg in terms of expanding the clinical utility of genomic profiling. I believe we can still do more to exploit this promising new technology and provide personalized care to improve the way we treat this disease.

A better understanding of the genomic characteristics of a tumor can impact the entire ecosystem of cancer care, inform clinical trial enrollment, and expand research directions.

Precision medicine is already helping deliver improved care for many types of cancer. With new genomic insights, we could help usher in a new era of treatment options for ovarian cancer.

LAURA L. HOLMAN, MD, MS, is Assistant Professor, Section of Gynecologic Oncology in the Stephenson Cancer Center at the University of Oklahoma Health Sciences Center, Oklahoma City.

Laura L

Laura L

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