Partnering olaparib with chemotherapy helps treat BRCA breast cancers

A clinical trial for early-stage breast cancer patients with BRCA gene mutations has reported 100% survival after three years – and it’s all down to a subtle but significant change in the timing of the treatment

The researchers behind our phase 3 PARTNER trial stopped BRCA-linked breast cancers growing or coming back by combining the targeted drug olaparib with chemotherapy before surgery. 

By giving patients olaparib tablets 48 hours after each chemotherapy dose, the research team were able combine the strengths of the different drugs, putting more pressure on cancer cells while minimising side effects. 

All 39 of the patients who received the new combination survived at least three years after surgery. Those results, published today in Nature Communications, suggest olaparib and chemotherapy could become the best treatment option for breast cancers caused by inherited BRCA mutations.

Professor Jean Abraham, who led the trial at Addenbrooke’s Hospital in Cambridge, said: “It’s rare to have a 100% survival rate in a study like this, and for these aggressive types of cancer. 

“We’re incredibly excited about the potential of this new approach, as it’s crucial that we find a way to treat and hopefully cure patients who are diagnosed with BRCA1 and BRCA2 related cancers”. 

Although more studies will be needed to validate the findings in a larger group of patients, the same approach could also be used to treat other cancers linked to BRCA mutations. 

BRCA mutations and breast cancer treatment

Around 1 in 50 breast cancers are caused by BRCA gene mutations, which can run in families.

We all have BRCA genes (“breast cancer” genes) in our cells. They contain crucial instructions for repairing our DNA when it gets damaged. The problem begins in the rare cases when those genes become faulty and lose the ability to carry out repairs, increasing people’s risk of breast cancer, ovarian cancer and prostate cancer, among some other cancer types. 

Olaparib is designed to target specific weaknesses in cancers caused by BRCA mutations. For early-stage breast cancers, it’s currently used after surgery (as an ‘adjuvant’ treatment) to target any remaining breast cancer cells and reduce the risk of the cancer coming back.

Although olaparib and other PARP inhibitors are some of our best treatments for BRCA-mutated cancers, doctors have never before had a safe and effective way of using them before surgery (as a ‘neoadjuvant’). Instead, they use combinations of chemotherapy and immunotherapy to shrink and contain the tumour and help make sure surgeons can completely remove it.  

Partners in time

Before PARTNER, it wasn’t possible to add PARP inhibitors to chemotherapies before surgery because of the risk of causing significant damage to people’s bone marrow – leading to very serious side effects. 

A chance conversation between Professor Abraham, who wanted to help more patients benefit from olaparib, and Mark O’Connor, chief scientist at Astrazeneca, who was researching how it interacts with chemotherapy, revealed the way forward. 

Together, they designed the PARTNER trial to test whether spacing out chemotherapy and olaparib before surgery could make it possible to safely combine their strengths. 

Almost 10 years on, their results show that giving olaparib tablets 48 hours after each dose of chemotherapy leads to better outcomes for women with early stage breast cancers caused by BRCA mutations. The researchers believe this is because it gives bone marrow time to recover from chemotherapy while leaving cancer cells vulnerable.

All 39 PARTNER patients who received chemotherapy followed by olaparib survived for the critical three years after surgery, where the risk of relapse and death is highest. Only one person relapsed.

That 100% three-year survival compares to 88% for people in PARTNER’s control arm, who just received the standard chemotherapy. Nine of these 45 patients relapsed, and six died.

Next steps

The team are now planning a larger, multinational trial with 600 patients to validate their results.

Michelle Mitchell, our chief executive, said: “One of the best ways that we can beat cancer sooner is by making more effective use of treatments that are already available to us. 

“While this research is still in its infancy, it is an exciting discovery that adding olaparib at a carefully-timed stage of treatment can potentially give patients with this specific type of breast cancer more time with their loved ones. 

“Research like this can help us find safer and kinder ways to treat certain types of cancer.”