LUGANO, Switzerland - A novel combination of well-known drugs prolongs survival in patients with hormone/castration-sensitive prostate cancer, according to late breaking research presented at the ESMO Congress 2021. (1,2) The PEACE-1 and STAMPEDE studies found that the addition of abiraterone acetate plus prednisolone (AAP) to standard therapy lengthened survival compared to standard therapy alone.
Commenting on the findings, Dr. Maria De Santis, Chair of Interdisciplinary Urological Oncology, Department of Urology, Charité Universitätsmedizin, Berlin, Germany said: “The findings have the potential to be implemented in our daily practice right away as we do not have to wait for the approval of a new drug. The clearly positive results are reassuring and should convince patients and physicians to intensify the treatment of patients with metastatic and high-risk locally advanced hormone/castration-sensitive prostate cancer early on. I expect this kind of treatment intensification to be implemented as a standard of care.”
For men with metastatic prostate cancer, androgen deprivation therapy (ADT) was the standard of care for decades. In 2015, docetaxel (a chemotherapy agent) was shown to improve survival when added to ADT and in 2017, abiraterone (a next generation hormonal agent) was also shown to improve survival when added to ADT. Until now, though, it was unknown whether one or both agents should be added to ADT to achieve the best outcomes. PEACE-1 found that using three drugs upfront is better than just two in men with metastatic prostate cancer, not only to postpone cancer progression, but also to prolong life. When AAP was added to ADT and docetaxel, men experienced an additional 25% reduction in the risk of death compared to ADT and docetaxel alone.
Study author Prof. Karim Fizazi, Medical Oncologist, Institute Gustave Roussy and Professor in Oncology, University of Paris-Saclay, Villejuif, France said: “PEACE-1 is the first trial to establish that triplet treatment should be offered to these men, especially those with the most aggressive cancers (those with multiple metastases). Moreover, additional side-effects with the triplet combination were mostly mild, with very few severe side-effects.”
Fizazi pointed out that for men with high-burden metastatic prostate cancer, the triplet treatment used in PEACE-1 provided 2.5 additional years without cancer progression and approximately 18 additional months of life. “For the first time these men can expect to live more than five years whereas before 2015 their median survival was less than three years. By 2022 all three treatments will be generic drugs which should improve access for patients worldwide.”
Fizazi noted that more follow-up is required in men with low-burden metastatic prostate cancer to accurately assess survival. “Triplet systemic treatment clearly postponed cancer progression in these patients but we need more time to determine whether it improves survival. This also applies to the role of local radiotherapy directed to the primary prostate cancer where we need longer follow-up to establish whether and how to best combine it with systemic treatments.”
STAMPEDE focused on non-metastatic (no spread visible on conventional scans) but high-risk (of spread) prostate cancer. Approximately 20% of localised prostate cancers are high-risk at diagnosis but account for the majority of relapses and consequently deaths in this population. Androgen deprivation is given for two or three years and combining it with local radiotherapy to the prostate and pelvis improves life expectancy. Adding treatments such as docetaxel chemotherapy has been tested and shown to prolong time to relapse but did not prolong life expectancy.
The trial found that at six years, men who had received standard treatment plus AAP for two years had an improvement in metastasis-free survival from 69% to 82%, an improvement in overall survival from 77% to 86% and an improvement in prostate cancer specific survival from 85% to 93% – compared to standard treatment alone.
Study author Prof. Gerhardt Attard, John Black Charitable Foundation Endowed Chair in Urological Cancer Research at University College London, UK said: “Based on these results, all men with high-risk non-metastatic prostate cancer should be considered for two years of abiraterone. This will involve more hospital visits during this period to manage administration of the drug but by reducing subsequent relapse, may reduce the overall burden for both patients and health services.”
Attard noted that more information is needed on the optimal length of AAP therapy. “We did not study different durations of treatment so administering AAP for a shorter time may be equivalent and longer may be even more effective.”
Comparing these results with the current treatment options, De Santis said: “The survival benefit in PEACE-1 is a clear improvement and adds to the advances recently made for patients with metastatic hormone/castration sensitive prostate cancer. With regards to the non-metastatic patients in STAMPEDE, this is a completely new patient group that has not been included in other published trials. The addition of systemic treatment with AAP for at least two years in this population will change our former treatment strategy which has been only ADT plus or minus radiotherapy to the prostate for many years.”
Notes to Editors
Please make sure to use the official name of the meeting in your reports: ESMO Congress 2021
Official Congress Hashtag: #ESMO21
Disclaimer
This press release contains information provided by the authors of the highlighted abstracts and reflects the content of these abstracts. It does not necessarily reflect the views or opinions of ESMO who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct.
References
- LBA4_PR ‘Abiraterone acetate plus prednisolone (AAP) with or without enzalutamide (ENZ) added to androgen deprivation therapy (ADT) compared to ADT alone for men with high-risk non-metastatic (M0) prostate cancer (PCa): Combined analysis from two comparisons in the STAMPEDE platform protocol‘ will be presented by Gerhardt Attard during Presidential Symposium 2 on Sunday, 19 September, 15:05 to 16:37 (CEST) on Channel 1. Annals of Oncology, Volume 32, 2021 Supplement 5
- LBA5_PR ‘A phase 3 trial with a 2x2 factorial design in men with de novo metastatic castration-sensitive prostate cancer: overall survival with abiraterone acetate plus prednisone in PEACE-1‘ will be presented by Karim Fizazi during Presidential Symposium 2 on Sunday, 19 September, 15:05 to 16:37 (CEST) on Channel 1. Annals of Oncology, Volume 32, 2021 Supplement 5
K. Fizazi1, J. Carles Galceran2, S. Foulon1, G. Roubaud3, R. McDermott4, A. Fléchon5, B. Tombal6, S. Supiot7, D.R. Berthold8, P. Ronchin9, G. Kacso10, G. Gravis Mescam11, F. Calabro'12, J.F. Berdah13, A. Hasbini14, M. Silva15, A. Thiery-Vuillemin16, I. Latorzeff17, I. Rieger18, A. Bossi19
1Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Saclay, Villejuif, France, 2Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain, 3Medical Oncology, Institute Bergonié, Bordeaux, France, 4Oncology (Medical Oncology), St Vincent's University Hospital and Cancer Trials Ireland, Dublin, Ireland, 5Department of Medical Oncology, Centre Léon Bérard, Rhones-Alpes, France, 6Urology, Cliniques Universitaires St. Luc - Université Catholique de Louvain, Brussels, Belgium, 7Radiotherapy, ICO Institut de Cancerologie de l'Ouest René Gauducheau, Saint-Herblain, France, 8Medical Oncology Department, CHUV - Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 9Radiotherapy, Centre Azuréen de Cancérologie, Mougins, France, 10Medical Oncology, Amethyst Radiotherapy Center, Bucharest, Romania, 11Medical Oncology Dept., IPC - Institut Paoli-Calmettes, Marseille, France, 12Medical Oncology, Azienda Ospedaliera S. Camillo Forlanini, Rome, Italy, 13Medical Oncology, Clinique Sainte-Marguerite, Hyères, France, 14Medical Oncology, Clinique Pasteur Lanroze, Brest, France, 15Radiotherapy, Centre François Baclesse, Caen, France, 16Medical Oncology, Centre Hospitalier Universitaire de Besançon, Besançon, France, 17Radiation Oncology, Clinique Pasteur, Toulouse, France, 18Clinical Research, Unicancer, Kremlin-Bicêtre, France, 19Radiation Oncology, Institut Gustave Roussy, University of Paris Saclay, Villejuif, France
Background: Since 2015, combining androgen deprivation therapy (ADT) with either docetaxel, androgen signaling inhibitors (ASI), or radiotherapy to the primary tumor (RXT) (for low metastatic burden) was shown to improve overall survival (OS) and has thus become the new standard of care (SOC) in men with mCSPC. It is unknown whether combining those treatments on top of ADT could further increment outcomes. PEACE-1 is a phase 3 trial with a 2x2 factorial design of abiraterone acetate plus prednisone (abiraterone) and/or local radiotherapy. First results show that adding abiraterone to ADT+docetaxel significantly improves rPFS in men with mCSPC (HR: 0.50 (0.40-0.62), p<0.0001) (Fizazi, ASCO 2021).
Methods: 1173 men (57% high-, 43% low-volume) with de novo mCSPC were randomized to SOC, SOC+abiraterone, SOC+RXT or SOC+abiraterone+RXT (SOC was ADT+docetaxel for 710 pts). The overall type I error testing the abiraterone effect was 5% (4.9% for OS, 0.1% for rPFS). In the ADT+docetaxel population, 249 events were required to detect an HR of 0.70 for OS with 80% power.
Results: The median follow-up is 4.4 yrs (n=273 death events in the ADT+docetaxel population). The effect of abiraterone on OS did not interact with the one of RXT (p=0.82) allowing to pool the abiraterone arms together for comparison. OS was improved by abiraterone both in the overall population (HR: 0.83, 95% CI: 0.69-0.99, p=0.034; medians: 5.7 vs 4.7 yrs) and in the ADT+docetaxel population (HR: 0.75, 95% CI: 0.59-0.96, p=0.021; medians: NR vs 4.4 yrs). Among the ADT+docetaxel pts who developed CRPC, 231/263 (88%) then received at least one life-prolonging therapy and 222/263 (84%) at least one ASI in the control arm, compared to 110/141 (78%) and 67/141 (48%) in the abiraterone arm, respectively. Grade 3-5 adverse events reported in >5% of pts in the ADT+docetaxel population included neutropenic fever (5% vs 5%), neutropenia (10% vs 9%), liver toxicity (6% vs 1%) and hypertension (21% vs 13%) in the abiraterone and control arms, respectively.
Conclusions: Adding abiraterone to ADT plus docetaxel improves both rPFS and OS in mCSPC men, even when 84% of mCRPC men from the control arm receive an ASI.
Clinical trial identification: NCT01957436.
Editorial acknowledgement: We thank Sébastien Marion from Unicancer for editing the English.
Legal entity responsible for the study: Unicancer
Funding: Janssen Pharmaceutical NV, Ipsen, Sanofi, PHRC
Disclosure: K. Fizazi: Financial Interests, Institutional, Advisory Board, null: Astellas; Financial Interests, Institutional, Invited Speaker, null: Astellas; Financial Interests, Institutional, Advisory Board, null: Bayer; Financial Interests, Institutional, Invited Speaker, null: Bayer; Financial Interests, Personal, Advisory Board, null: Curevac; Financial Interests, Institutional, Advisory Board, null: Janssen; Financial Interests, Institutional, Invited Speaker, null: Janssen; Financial Interests, Personal, Advisory Board, null: Orion; Financial Interests, Institutional, Invited Speaker, null: Sanofi; Financial Interests, Institutional, Advisory Board, null: AAA; Financial Interests, Institutional, Advisory Board, null: MSD; Financial Interests, Institutional, Invited Speaker, null: MSD; Financial Interests, Institutional, Advisory Board, null: AstraZeneca; Financial Interests, Institutional, Invited Speaker, null: AstraZeneca; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer; Financial Interests, Institutional, Research Grant, Trial chair: Bayer; Financial Interests, Institutional, Research Grant, Trial chair: AstraZeneca; Financial Interests, Institutional, Research Grant, Trial chair: Orion; Financial Interests, Institutional, Research Grant, Trial chair: MSD; Financial Interests, Institutional, Research Grant, Trial chair: BMS; Financial Interests, Institutional, Research Grant, Trial chair: Janssen.
J. Carles Galceran: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Astrazeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Astellas; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Janssen.
G. Roubaud: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Astrazeneca; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Pfizer.
R. McDermott: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: Clovis; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Regeneron.
A. Fléchon: Financial Interests, Personal, Expert Testimony: AAA; Financial Interests, Personal, Expert Testimony: Astrazeneca; Financial Interests, Personal, Expert Testimony: Astellas; Financial Interests, Personal, Expert Testimony: Bayer; Financial Interests, Personal, Expert Testimony: Janssen; Financial Interests, Personal, Expert Testimony: Novartis; Financial Interests, Personal, Expert Testimony: Sanofi.
B. Tombal: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Ferring; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Myovant; Financial Interests, Personal, Advisory Board: Sanofi.
S. Supiot: Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Bouchara; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Institutional, Principal Investigator: Astrazeneca; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Institutional, Principal Investigator: Janssen.
D.R. Berthold: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche.
G. Kacso: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Astrazeneca; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Astrazeneca; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Invited Speaker: MSD.
G. Gravis Mescam: Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Merck; Financial Interests, Institutional, Advisory Board: AAA; Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Janssen; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Sanofi.
F. Calabro': Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Astrazeneca; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Pfizer.
A. Thiery-Vuillemin: Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Astrazeneca; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Astellas.
I. Latorzeff: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Janssen.
A. Bossi: Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Bard; Financial Interests, Personal, Advisory Role: Elekta; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Myovant; Financial Interests, Personal, Speaker’s Bureau: Astellas; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Ferring; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Invited Speaker: Janssen.
All other authors have declared no conflicts of interest.
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