Triple therapy shows major benefits in the treatment of metastatic prostate cancer

Dr. Joan Carles
  • A study performed by the European PEACE consortium, in which the Vall d’Hebron Institute of Oncology (VHIO), part of the Vall d’Hebron Campus, participated, has shown how adding abiraterone to androgen deprivation therapy and docetaxel improves both radiographic progression-free survival and overall survival.
  • This triple therapy could become the standard treatment for patients with de novo metastatic cancer with a high metastatic load.
  • The results of the study have just been published in the journal The Lancet, while preliminary data were released in a plenary session at the last annual congress of the European Society for Medical Oncology (ESMO).

Barcelona, April 9th, 2022 – After several decades with no substantial progress in the treatment of de novo metastatic hormone-sensitive prostate cancer (where the cancer has already metastasised at the time of diagnosis), in the last 10 years there has been a treatment revolution, by adding a variety of treatments to androgen deprivation therapy which, until recently, was the standard for treating these tumours. Now, for the first time, it has been shown that a systemic triple therapy can improve progression-free survival and overall survival in these patients and it promises to become the new standard of care. The study data that support this triple therapy have been published in the journal The Lancet.

Specifically, the European PEACE consortium carried out a study to assess the safety and efficacy of adding abiraterone, a second-generation antiandrogen drug, and prednisone to the combined therapy of androgen deprivation and docetaxel, a chemotherapy drug. “This is the first trial to show that a triple systemic therapy improves results in de novo metastatic prostate cancer patients. These findings, combined with evidence from other studies, support the idea that early intensification of treatment is more effective than treatments used sequentially when the disease becomes more resistant”, claims Dr. Joan Carles, one of the authors of the published article and head of the Genitourinary, CNS and Sarcoma Tumour Group of the Vall d’Hebron Institute of Oncology (VHIO), part of the Vall d’Hebron Campus.

The data collected in the study, which has now been published in the journal The Lancet, had already been released at the plenary session of the annual European Society for Medical Oncology (ESMO) congress, held in October 2021. A total of 1,173 patients took part in the study, divided into different groups to find which combination of new therapies provided the best result.

Improvement in progression-free and overall survival

The different treatments tested in the study were not new, as they had proved to be effective in managing metastatic patients with castration-resistant and hormone-sensitive prostate cancer in previous studies. The difference was that, for the first time, their combined use was considered from the start and not sequentially, as has been the case up to now. “And the combination we have found that produces the best result is the one in which abiraterone is administered in combination with prednisone together with androgen deprivation and docetaxel. One can see how the risk of disease progression is reduced by 50% with this combination, from an average of 2.05 years without progression to 4.46, while the risk of mortality also drops by 25%”, stresses Dr. Joan Carles, is also Section Head and head of the Genitourinary, Central Nervous System, Sarcoma and Tumours of Unknown Origin Unit at Vall d’Hebron University Hospital, part of the Vall d’Hebron Campus. He further highlighted that this has been achieved with a manageable and acceptable increase in toxicity.

Thus, the 36-month survival obtained with androgen deprivation was extended to 42 months by adding chemotherapy, and to 53 months when this treatment was combined with abiraterone. As Dr. Joan Carles further explains, “Now, with the triple combination, this has reached 60 months. A very good figure if one considers that 85% of the patients who progressed to become castration-resistant in the control arm were administered drugs that had been shown to increase survival in this situation, so these figures could have been even higher if this were not the case”. Joan Carles.

Reaching clinical practice

The fact that the drugs used have already been approved for the treatment of the disease is a further point worth stressing. “We could implement it in our clinical practice immediately, as they are drugs that have been approved separately for this therapeutic indication. The clearly positive results are encouraging and should favour interaction between different specialities to eventually benefit high-risk, hormone-sensitive metastatic prostate cancer patients”, adds Dr. Joan Carles.

A route for new research

The study by the PEACE consortium focussed on de novo metastatic prostate cancer patients, so it is not clear whether this triple therapy could benefit metachronous patients, i.e. those in whom metastatic lesions appear some time after an initial cancer diagnosis. As Dr. Joan Carles adds, “At the very least, patients with a high metastatic load who are sufficiently fit to be treated with docetaxel must be considered for this systemic triple therapy. It should be stressed that abiraterone has been approved for metastatic prostate cancer in many countries and will soon become a generic drug around the world”.

Another doubt that needs to be cleared up is whether the combination of intensive first-line systemic treatment with radiotherapy for the primary tumour could provide additional clinical benefits for metastatic prostate cancer patients. “This further analysis will be conducted when the previously planned number of general and progression-free survival events is reached among the male population with low-volume metastatic dissemination”, concludes Dr. Joan Carles.

References:

Karim Fizazi, Stéphanie Foulon, Joan Carles, Guilhem Roubaud, Ray McDermott, Aude Fléchon, Bertrand Tombal, Stéphane Supiot, Dominik Berthold, Philippe Ronchin, Gabriel Kacso, Gwenaëlle Gravis, Fabio Calabro, Jean-François Berdah, Ali Hasbini, Marlon Silva, Antoine Thiery-Vuillemin, Igor Latorzeff, Loïc Mourey, Brigitte Laguerre, Sophie Abadie-Lacourtoisie, Etienne Martin, Claude El Kouri, Anne Escande, Alvar Rosello, Nicolas Magne, Friederike Schlurmann, Frank Priou, Marie-Eve Chand-Fouche, Salvador Villà Freixa, Muhammad Jamaluddin, Isabelle Rieger, Alberto Bossi, on behalf of the PEACE-1 investigators*. “Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design”. The Lancet. April 08, 2022. DOI: https://doi.org/10.1016/S0140-6736(22)00367-1