According to significant clinical research, a medicine previously approved for the treatment of breast and ovarian cancers is more successful than targeted hormone therapy at keeping cancer at bay in certain men with advanced prostate cancer.
Olaparib, a tablet without the side effects of chemotherapy, may be able to target a deficiency in prostate tumors’ ability to repair damaged DNA. It’s on the verge of being approved as the first genetically targeted prostate cancer treatment.
This precision medicine therapy, a PARP inhibitor, which selectively targets cancer cells with defective DNA repair genes, inhibited prostate cancer growth more efficiently than abiraterone and enzalutamide, two current targeted hormone treatments.
The PROfound trial’s final results, which were published in the New England Journal of Medicine today (April 20, 2020), are expected to pave the way for olaparib’s approval in prostate cancer in the United States and Europe later this year. AstraZeneca supported the research.
387 men with advanced prostate cancer who had alterations in one or more of 15 DNA repair genes were studied by a team from The Institute of Cancer Research in London and The Royal Marsden NHS Foundation Trust, along with colleagues from all over the world, including Northwestern University in Chicago, US. The use of olaparib in this group of men with defective DNA repair genes considerably slowed disease progression, according to the researchers.
Our findings show that olaparib a drug which targets an Achilles heel in cancer cells while sparing normal, healthy cells can outperform targeted hormone treatments in some men with advanced prostate cancer. It’s exciting to see a drug which is already extending the lives of many women with ovarian and breast cancer now showing such clear benefits in prostate cancer too.
Johann de Bono
Men with defective BRCA1, BRCA2, or ATM genes gained the most from olaparib, with their disease progressing 7.4 months after treatment, compared to 3.6 months for those who received enzalutamide and abiraterone.
Olaparib was also beneficial to men who had mutations in any of the other 12 pre-selected DNA repair genes.
Overall, men who were administered olaparib for any of the 15 defective DNA repair genes waited 5.8 months on average before their cancer worsened, compared to 3.5 months with targeted hormone treatment.
The Institute of Cancer Research’s (ICR) discovery of abiraterone, as well as the ICR’s and The Royal Marsden’s development of the drug, has revolutionized treatment for men with advanced prostate cancer.
The possibility that olaparib, which the ICR learned how to genetically target, could be even more effective than abiraterone in chosen males with DNA repair defects excites researchers.
Despite the fact that more than 80% of men who received targeted hormone treatments switched to olaparib when their cancer progressed and spread, overall survival for men with faulty BRCA1, BRCA2, or ATM genes was 19 months on average for those who received olaparib, compared to 15 months for those who received abiraterone or enzalutamide.
Longer follow-up will be required to definitively indicate a survival improvement. Anemia and nausea were the most common side effects, both of which have previously been linked to olaparib. Overall, though, olaparib is a well-tolerated medication that is far less harsh on patients than chemotherapy.
The PROfound trial is the first to demonstrate the importance of genetic testing in prostate cancer patients. Different patient groups must be identified based on their genetics, and treatment must be tailored accordingly.
Within the next two years, researchers hope to see olaparib available on the NHS for patients with advanced prostate cancer and defective DNA repair genes.
They’ll then investigate into combining olaparib with other medications to see if they may improve results even further.
Study co-leader Professor Johann de Bono, Professor of Experimental Cancer Medicine at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said:
“Our findings show that olaparib a drug which targets an Achilles heel in cancer cells while sparing normal, healthy cells can outperform targeted hormone treatments in some men with advanced prostate cancer. It’s exciting to see a drug which is already extending the lives of many women with ovarian and breast cancer now showing such clear benefits in prostate cancer too.”
“I can’t wait to see this drug start reaching men who could benefit from it on the NHS hopefully in the next couple of years. Next, we will be assessing how we can combine olaparib with other treatments, which could help men with prostate cancer and faulty DNA repair genes live even longer.”
Peter Isard, 59, a patient at The Royal Marsden, said:
“Initially after diagnosis, I went onto hormone therapy and then chemotherapy. Six months after finishing chemotherapy, my PSA rose rapidly and I was told my chance of living for two years would be quite low. I came to The Royal Marsden for a second opinion and Prof de Bono found I had a genetic mutation that would make me suitable for an olaparib trial.”
“I’ve been on the drug for almost two years now. I had a number of tumours in my lymph nodes, but now there is only one that is visible and I feel incredibly lucky not to have experienced any side-effects whatsoever.”
Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:
“It is great to see that this treatment, which we learned how to genetically targeted at the ICR, can successfully hit an Achiles heel in some men with advanced prostate cancer. These landmark findings mean that olaparib is now set to become the first ever genetically targeted drug for the disease.”
“The next step will be to find new ways to combine olaparib with other treatments in order to prevent or overcome drug resistance. It is this kind of research, which aims to target cancer’s lethal ability to adapt and evolve, which we will be conducting in our pioneering Centre for Cancer Drug Discovery once it opens later this year.”
