- Clinical trial results for olaparib, already used to treat ovary and breast cancer, support the first personalized prostate cancer treatment based on molecular tumor profiling
- Progression-free survival time for patients who used olaparib was almost double the control group figure, and other aspects, like the objective response rate and overall survival, also improved
- This treatment can now be included quickly and effectively in the therapeutic arsenal against prostate cancer, as the drug is already used in patients with other tumors
- Up to 20-25% of tumors in patients with metastatic prostate cancer show alterations to the target genes
Barcelona, April 29, 2020.– A drug used to treat breast and ovarian tumors can now be used in advanced metastatic prostate cancer patients after a new clinical trial. The PROfound trial has shown that olaparib, a PARP inhibitor, is effective in prostate cancer patients with certain molecular mutation profiles. One of the authors of the article setting out the results, just published in the New England Journal of Medicine, is Dr. Joaquín Mateo, principal investigator of the Prostate Cancer Translational Research Group at the Vall d’Hebron Institute of Oncology (VHIO) and oncologist at the Vall d’Hebron University Hospital, which has taken part in developing this drug from the beginning.
This study, at phase III of development, provides confirmation that olaparib is a treatment option for patients with prostate cancer with certain mutations in their tumor cells. For the first time, it shows the effectiveness of the molecular classification of tumors to help treatment choice and improve patient survival. “We are entering a new era when genomic tests will become part of managing patients with prostate cancer and this new therapy will be incorporated into the standard treatments for patients who have alterations in genes involved in repairing DNA. The fact that olaparib is already used for this type of mutation in other tumors has helped with its fast, effective development for prostate cancer,” said Dr. Mateo.
The randomized phase III trial recruited almost 400 patients with advanced metastatic prostate cancer in whom the disease had progressed under standard treatments. “To take part in this trial, all the patients had to have some alteration in their tumor in a series of pre-specified genes related to repairing DNA damage. These alterations make the tumor more aggressive but they also become its Achilles heel,” said Dr. Mateo. The olaparib results were compared with those for patients receiving a new hormone agent – either enzalumtamide or abiraterone, both regularly used in clinical practice.
Exploiting the cancer’s weaknesses
One way of treating cancer is to attack its weak points. Progress over the last few years has made it possible to characterize the different types and subtypes of tumor more precisely. This has been used to personalize treatments and improve results. The results of this latest clinical trial are part of this line of investigation.
Olaparib is a drug that inhibits the enzyme PARP, which helps repair DNA. Inhibiting it prevents the tumor cells repairing themselves and, as a result, they are destroyed. “Although cancer resistant to metastatic castration is a highly diverse disease, up to 25% of tumors show alterations in genes involved in DNA repair. It seemed a good idea to attack this target, as has now been seen with the results of the PROfound trial we have just published,” said Dr. Mateo.
The trial patients were split into two groups or cohorts. One of them, cohort A, consisted of 245 patients showing alterations in the BRCA1 and BRCA2 genes, which are part of the mechanism for repairing damaged DNA called “homologous recombination”, or the ATM gene, which detects damage to DNA and activates repairs to it. The other group, called cohort B, consisted of 142 patients with some sort of alteration in any of the other 12 selected genes also related to DNA repair but with a less well-known impact on the tumor. Before they took part in the study, a sequencing test was carried out on a biopsy of the patients’ tumors to find out if they had these mutations.
“The best results have been obtained in patients with alterations to the BRCA genes, who obtained the greatest benefits. But we have also seen effects on the other alterations, and this is very important. More detailed analyses are still being carried out but olaparib’s action in these patients is very promising,” said Dr. Mateo. He pointed out that results with metastatic-resistant prostate cancer are generally very poor.
Improving progression-free survival time
One of the parameters measured in this trial is progression-free survival time. In this sense, the results in cohort A were very positive as this time was almost doubled, from 3.55 months in the control group to 7.39 months in cohort A. Significant benefits were also seen in the objective response rate and in the time to pain progression.
The results of this trial have demonstrated the validity of using olaparib, as it has managed to reduce the risk of disease progression or death to 66%. “The average overall survival time also increased from 15.11 to 18.5 months. It should be taken into account that more than 80% of patients who were receiving the hormone treatment when the disease progressed were allowed to go into the olaparib group. This means the detection of the improvement is an even more convincing factor in showing that the drug helps these patients,” said Dr. Mateo. “This trial validates the data from two previous smaller trials in which we could already see promising data on olaparib’s anti-tumor activity. With this confirmation we believe we have enough evidence for incorporating genomic tests and olaparib treatment into the standard management of advanced stages of prostate cancer.”