In research aimed at changing the treatment of advanced prostate cancers, a new drug combination has halted disease progression in men with aggressive tumors.
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Among the patients who have received the new therapy, all with metastases, 77% maintained cancer without progression at three years. Among patients who received standard therapy, the percentage dropped to 56%.
Mortality at three years was also lower with the new therapy (22%) than with standard therapy (28%), although the difference is not yet statistically significant.
77% of patients with metastases maintain cancer without progression after three years
The results are presented today at the American Society of Clinical Oncology congress held in Chicago, which with more than 40,000 participants is the largest cancer congress in the world. They have been simultaneously published in the journal The New England Journal of Medicine.
The new therapy combines two drugs already approved in Europe and the United States, which will facilitate rapid adoption, reports Joaquín Mateo, head of the Prostate Cancer Group at the Vall d’Hebron Institute of Oncology (VHIO) in Barcelona and one of the six members of the international clinical trial steering team. “It will change the way we treat advanced prostate cancer,” Mateo tells La Vanguardia.
One of the two drugs is an inhibitor of male hormones like testosterone, which drive prostate cancer progression. This product, enzalutamide, is already approved for most cases where the disease is advanced.
The other drug, which is the major novelty of the new therapy, causes tumor cell death with a strategy called synthetic lethality. It is talazoparib, which causes failure in cancer cells that prevents them from surviving.
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The key is that cells have specialized genes to repair their DNA. These genes can fail when mutated, but cells still have the PARP enzyme to repair their DNA in these cases. If the PARP enzyme is attacked with a drug like talazoparib, and there is also damage in the repair genes, then the accumulated DNA damage leads to cell death.
“A genomic analysis of all patients from the moment of diagnosis will be necessary,” says Joaquín Mateo
PARP inhibitors are only effective in patients with mutations in DNA repair genes, which represent 25% of metastatic prostate cancers. But among the different prostate cancer subtypes, these are particularly aggressive, and therefore in need of more effective treatments.
With about 6,000 annual deaths in Spain, prostate cancer is the third leading cause of mortality in the male population after lung and colorectal cancers, according to data from the Spanish Society of Medical Oncology (SEOM). Considering that one in four metastatic cases have mutations in DNA repair genes, the new therapy may be indicated for more than a thousand men per year in Spain.
“A genomic analysis of all patients from the moment of diagnosis will be necessary,” says Joaquín Mateo. This way, treatment with PARP inhibitors can be offered to patients who can benefit from these drugs. “Probably this same year the international clinical practice guidelines will be updated” to incorporate these advances, adds the oncologist from Vall d’Hebron hospital.
In the clinical trial, started in 2021 and continuing until August 2027, 599 patients from 27 countries with an average age of 70 years have participated. Half received the combined therapy of enzalutamide and talazoparib, while the other half received only enzalutamide. Spain, with 55 patients, is one of the countries with the most participants.
The most common side effect among people treated with talazoparib has been anemia, which required a median of two blood transfusions per patient throughout the treatment.
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