What Is Platinum-Resistant Ovarian Cancer?

Platinum is a silver-colored precious metal. Most people are familiar with it as a metal used for jewelry. But platinum is also a key part of some cancer treatments.

Cisplatin and carboplatin are 2 kinds of chemotherapy treatments that include platinum (platinum-based therapies). They are both used to treat ovarian cancer. They are so important that some doctors call them the backbone of ovarian cancer treatment.^1,2

What does it mean to have "platinum-resistant" cancer?

Some people with cancer have success with platinum-based cancer treatments. But if their cancer returns after treatment with platinum, the cancer is called platinum resistant.¹

About 1 in 4 people with ovarian cancer may also have a natural resistance to platinum. This means platinum-based cancer treatments will not work on them, even the first time. But platinum resistance more commonly happens after a platinum-based cancer treatment works at first.²

Your doctor also may use the term "platinum-sensitive" cancer. In platinum-resistant cancer, the tumor has no response to a treatment. In platinum-sensitive cancer, the tumor's response is too small to be effective in treating the cancer.³

Knowing whether a cancer is resistant to platinum helps doctors choose the next treatment to try. Because some cancers are platinum resistant, more safe and effective ovarian cancer treatment options that do not include platinum are needed.^1,2

How is platinum-resistant ovarian cancer treated?

There are several options when an ovarian cancer no longer responds to platinum-based treatments. One approach is to try an immunotherapy or immunomodulatory drug. These types of treatment direct the body's own immune system to find and destroy cancer cells.⁴

Another approach is to use combinations of chemotherapy drugs. For example, 1 clinical trial is testing a combination of gemcitabine and adavosertib. Both of these drugs damage or interrupt DNA processes of cancer cells, causing the cells to die. But they work in different ways.^2,5-8

A third approach is to combine a chemotherapy drug with a poly ADP-ribose polymerase (PARP) inhibitor. PARPs are proteins that work to fix damaged DNA, which helps cancer cells live. PARP inhibitors prevent these proteins from working properly. As a result, the DNA damage piles up and the cancer cell is more likely to die.^9-11

Other treatment options include:¹²

1. Single-agent chemotherapy
2. Targeted therapy
3. Hormone therapy

What is a cancer biomarker?

Genes, proteins, and genetic changes that give information about a cancer are called biomarkers. Certain types of tests allow doctors to look for cancer biomarkers. Sometimes this can be helpful for choosing a treatment. These tests include:¹³

• Tumor genetic testing or sub-typing
• Genomic profiling or genomic sequencing
• Molecular testing or profiling
• Next-generation sequencing

Some biomarkers are important when choosing a treatment for platinum-resistant cancer. Current care guidelines recommend testing for the following biomarkers in this situation:¹²

1. BRCA-1 and BRCA-2 gene status
2. Homologous recombination repair (HR) status
3. Microsatellite instability (MSI)
4. Mismatch repair (MMR)
5. Tumor mutational burden (TMB)
6. BRAF (gene that codes the B-raf protein)
7. NTRK (neurotrophic receptor tyrosine kinase)

How do biomarkers help doctors decide on the right treatment for me?

Biomarkers help your doctor choose between many treatment options. Some treatments work better if a person has, or does not have, a specific biomarker. These biomarkers are also important targets for new drugs that are being developed to help people with platinum-resistant ovarian cancer.³

Which biomarkers are linked to treatments in ovarian cancer?

People with BRCA mutations tend to respond to platinum-based treatments at first. Then the cancer becomes resistant. But PARP inhibitor treatments tend to work well in these cases if the person also has certain HR mutations. And people who have ovarian cancer that has a high TMB load are more likely to have good results from an immunotherapy called an immune checkpoint inhibitor.³

People with BRAF biomarkers and platinum resistance may receive dabrafenib and trametinib. These treatments block signals in solid tumor cells that help the tumor grow. Entrectinib or larotrectinib may be used if a tumor has a NTRK biomarker. These targeted treatments interrupt cancer cell signals. This then leads the cancer cells to die.^12,14,15

This is not a complete list of biomarkers and therapies for ovarian cancer. Every cancer and person with cancer is unique. Talk to your doctor about whether you might benefit from genetic testing to help in choosing a treatment.