Olaparib: A New Hope for BRCA Patients with Ovarian Cancer

By Charles Li MD

January 06, 2019

  • Advanced Ovarian Cancer has been one of the deadliest forms of cancer for women.

  • Even with surgery and chemotherapy, most patients will quickly relapse.

  • In one of the biggest clinical trials to date for Olaparib and PARP Inhibitors, nearly 60% of patients were still relapse free after 3 years compared to 27% of patients who did not receive the drug.

Maintnence Olaparib efficacy data in advanced ovarian cancer

Olaparib has been shown to significantly increase survival in a mostly incurable type of cancer.

While early stage ovarian cancer is readily treatable, with response rates over 90%, advanced ovarian cancer, where the cancer has spread around the body, is very challenging to treat. Most patients will either progress or pass away from their disease within 5 years.

A new generation of drugs targeting the mechanism behind BRCA1/2 appears to offer new hope to advanced ovarian cancer patients carrying these mutations.

In a clinical trial recently published in the New England Journal of Medicine, researchers found that this new class of drug, PARP Inhibitors, may be extraordinarily effective in some ovarian cancer patients.

With the treatment, around 60% of patients with advanced ovarian cancer were still alive and progression-free three years after their surgery and chemotherapy, compared to 27% in the control group. This is a dramatic increase in survival in a cancer many considered incurable.

Additionally, as seen in the Survival Rate Comparison Chart, survival rates almost appear to level off towards the end of the treatment, suggesting that many of the 60% of patients who remained progression-free may continue to live for many years after the trial.

As this was a randomized controlled trial, the patients in the treatment group were randomly selected and closely matched the control group in most other significant characteristics which suggests that this result is mostly due to the effect of the new drug class.

Effect of BRCA1/2 Mutations

This new class of drug however have only been shown to work for patients with BRCA1/2 mutations.

Many women carry mutations in BRCA1/2, a tumor suppressor gene. These mutations dramatically increase their chances of getting breast and ovarian cancer.

While only 1-2% of women are expected to get ovarian cancer in their lifetime, nearly 44% of women with BRCA1 mutations will get ovarian cancer by age 80. BRCA2 is associated with a slightly less, but still dramatically elevated risk.

data on Ovarian cancer rates in BRCA1/2 mutation carriers over time in a chart

How BRCA1/2 Works

In the body, BRCA1/2 encode proteins that repair your damaged DNA.

As with any complex machine, DNA accumulates damage over time in the form of mutations. Fortunately, your body has many mechanisms to repair this damage. The vast majority of mutations are harmless and silently repaired.

However, patients with BRCA1/2 mutations have deficiencies in their ability to repair double stranded breaks in DNA. Over time, these mutations can accumulate. If these mutations are in genes associated with cancer, they can help form tumors, leading to the increase in Breast and Ovarian cancer rates we see in patients with BRCA1/2 mutations.

BRCA mechanism, how BRCA works

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